To see the other types of publications on this topic, follow the link: Metastatic progression.
Journal articles on the topic 'Metastatic progression'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Metastatic progression.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Roda, Niccolo’, Valentina Gambino, and Marco Giorgio. "Metabolic Constrains Rule Metastasis Progression." Cells 9, no. 9 (2020): 2081. http://dx.doi.org/10.3390/cells9092081.
Full textAbstract:
Metastasis formation accounts for the majority of tumor-associated deaths and consists of different steps, each of them being characterized by a distinctive adaptive phenotype of the cancer cells. Metabolic reprogramming represents one of the main adaptive phenotypes exploited by cancer cells during all the main steps of tumor and metastatic progression. In particular, the metabolism of cancer cells evolves profoundly through all the main phases of metastasis formation, namely the metastatic dissemination, the metastatic colonization of distant organs, the metastatic dormancy, and ultimately the outgrowth into macroscopic lesions. However, the metabolic reprogramming of metastasizing cancer cells has only recently become the subject of intense study. From a clinical point of view, the latter steps of the metastatic process are very important, because patients often undergo surgical removal of the primary tumor when cancer cells have already left the primary tumor site, even though distant metastases are not clinically detectable yet. In this scenario, to precisely elucidate if and how metabolic reprogramming drives acquisition of cancer-specific adaptive phenotypes might pave the way to new therapeutic strategies by combining chemotherapy with metabolic drugs for better cancer eradication. In this review we discuss the latest evidence that claim the importance of metabolic adaptation for cancer progression.
2
Morgans, Alicia K., Christopher Sweeney, Christopher J. D. Wallis, et al. "Progression patterns by types of metastatic spread, prostate-specific antigen (PSA), and clinical symptoms: Post-hoc analyses of ARAMIS." Journal of Clinical Oncology 40, no. 16_suppl (2022): 5044. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.5044.
Full textAbstract:
5044 Background: Darolutamide (DARO), a highly potent and structurally distinct androgen receptor inhibitor, prolonged metastasis-free survival by nearly 2 years and reduced the risk of death by 31% vs placebo (PBO) with a favorable tolerability profile in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS. We present post-hoc analyses of ARAMIS to evaluate the association between metastatic progression with prostate-specific antigen (PSA) and clinical progression and to describe the distribution of metastatic progression between groups. Methods: Pts with nmCRPC were randomized 2:1 to DARO (n=955) or PBO (n=554) while continuing androgen-deprivation therapy. Descriptive analyses were performed using the primary data cutoff (Sept 3, 2018) for the double-blind period. Post-baseline metastases were based on central review of conventional radiographic imaging every 16 weeks. PSA and pain progression were defined per primary analysis ( N Engl J Med. 2019;380:1235-46). Results: Metastatic progression was observed in 13.6% of DARO and 28.5% of PBO pts. Most pts had isolated progression as bone (DARO 46%, PBO 39%) or lymph node (32%; 40%) metastasis (Table). Pts with radiographic progression had shorter median time from initial diagnosis to study treatment (DARO 72.9, PBO 74.4 months) vs the overall ARAMIS population (86.2, 84.2 months). Of all pts with metastatic progression, baseline PSA levels (ng/mL) were similar in DARO (12.6) and PBO pts (15.1); DARO pts had lower median PSA before metastasis (16.7) vs PBO pts (48.0) and median absolute/relative PSA decrease from baseline of -0.7/-3.2% vs an increase for PBO pts of 29.5/181%. PSA progression before metastasis was observed in 55.6% (160/288) of pts, occurring in fewer DARO (45.4%) vs PBO pts (63.9%) (treatment difference 18.5%; nominal 95% CI 6.5%–30.6%). The median time between PSA progression and metastasis was 7.0 months with DARO vs 5.6 months with PBO. Pain progression before metastatic progression was rare and similar between groups (DARO 16.9%, PBO 17.7%). Conclusions: DARO significantly reduced risk of metastatic progression and improved overall survival vs PBO without changing the pattern of metastatic progression. Many pts with nmCRPC experienced metastatic progression without PSA progression, and pain progression was rare. These results support the use of imaging with PSA monitoring to properly identify disease progression in pts with nmCRPC. Clinical trial information: TBC. [Table: see text]
3
Morgans, Alicia K., Christopher Sweeney, Christopher J. D. Wallis, et al. "Progression patterns by types of metastatic spread, prostate-specific antigen (PSA), and clinical symptoms: Post-hoc analyses of ARAMIS." Journal of Clinical Oncology 40, no. 16_suppl (2022): 5044. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.5044.
Full textAbstract:
5044 Background: Darolutamide (DARO), a highly potent and structurally distinct androgen receptor inhibitor, prolonged metastasis-free survival by nearly 2 years and reduced the risk of death by 31% vs placebo (PBO) with a favorable tolerability profile in patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) in ARAMIS. We present post-hoc analyses of ARAMIS to evaluate the association between metastatic progression with prostate-specific antigen (PSA) and clinical progression and to describe the distribution of metastatic progression between groups. Methods: Pts with nmCRPC were randomized 2:1 to DARO (n=955) or PBO (n=554) while continuing androgen-deprivation therapy. Descriptive analyses were performed using the primary data cutoff (Sept 3, 2018) for the double-blind period. Post-baseline metastases were based on central review of conventional radiographic imaging every 16 weeks. PSA and pain progression were defined per primary analysis ( N Engl J Med. 2019;380:1235-46). Results: Metastatic progression was observed in 13.6% of DARO and 28.5% of PBO pts. Most pts had isolated progression as bone (DARO 46%, PBO 39%) or lymph node (32%; 40%) metastasis (Table). Pts with radiographic progression had shorter median time from initial diagnosis to study treatment (DARO 72.9, PBO 74.4 months) vs the overall ARAMIS population (86.2, 84.2 months). Of all pts with metastatic progression, baseline PSA levels (ng/mL) were similar in DARO (12.6) and PBO pts (15.1); DARO pts had lower median PSA before metastasis (16.7) vs PBO pts (48.0) and median absolute/relative PSA decrease from baseline of -0.7/-3.2% vs an increase for PBO pts of 29.5/181%. PSA progression before metastasis was observed in 55.6% (160/288) of pts, occurring in fewer DARO (45.4%) vs PBO pts (63.9%) (treatment difference 18.5%; nominal 95% CI 6.5%–30.6%). The median time between PSA progression and metastasis was 7.0 months with DARO vs 5.6 months with PBO. Pain progression before metastatic progression was rare and similar between groups (DARO 16.9%, PBO 17.7%). Conclusions: DARO significantly reduced risk of metastatic progression and improved overall survival vs PBO without changing the pattern of metastatic progression. Many pts with nmCRPC experienced metastatic progression without PSA progression, and pain progression was rare. These results support the use of imaging with PSA monitoring to properly identify disease progression in pts with nmCRPC. Clinical trial information: TBC. [Table: see text]
4
Park, Sun H., Shunsuke Tsuzuki, Kelly F. Contino, et al. "Crosstalk between bone metastatic cancer cells and sensory nerves in bone metastatic progression." Life Science Alliance 7, no. 12 (2024): e202302041. http://dx.doi.org/10.26508/lsa.202302041.
Full textAbstract:
Although the role of peripheral nerves in cancer progression has been appreciated, little is known regarding cancer/sensory nerve crosstalk and its contribution to bone metastasis and associated pain. In this study, we revealed that the cancer/sensory nerve crosstalk plays a crucial role in bone metastatic progression. We found that (i) periosteal sensory nerves expressing calcitonin gene–related peptide (CGRP) are enriched in mice with bone metastasis; (ii) cancer patients with bone metastasis have elevated CGRP serum levels; (iii) bone metastatic patient tumor samples express elevated calcitonin receptor-like receptor (CRLR, a CGRP receptor component); (iv) higher CRLR levels in cancer patients are negatively correlated with recurrence-free survival; (v) CGRP induces cancer cell proliferation through the CRLR/p38/HSP27 pathway; and (vi) blocking sensory neuron–derived CGRP reduces cancer cell proliferation in vitro and bone metastatic progression in vivo. This suggests that CGRP-expressing sensory nerves are involved in bone metastatic progression and that the CGRP/CRLR axis may serve as a potential therapeutic target for bone metastasis.
5
Seely, Kevin D., Amanda D. Morgan, Lauren D. Hagenstein, Garrett M. Florey, and James M. Small. "Bacterial Involvement in Progression and Metastasis of Colorectal Neoplasia." Cancers 14, no. 4 (2022): 1019. http://dx.doi.org/10.3390/cancers14041019.
Full textAbstract:
While the gut microbiome is composed of numerous bacteria, specific bacteria within the gut may play a significant role in carcinogenesis, progression, and metastasis of colorectal carcinoma (CRC). Certain microbial species are known to be associated with specific cancers; however, the interrelationship between bacteria and metastasis is still enigmatic. Mounting evidence suggests that bacteria participate in cancer organotropism during solid tumor metastasis. A critical review of the literature was conducted to better characterize what is known about bacteria populating a distant site and whether a tumor depends upon the same microenvironment during or after metastasis. The processes of carcinogenesis, tumor growth and metastatic spread in the setting of bacterial infection were examined in detail. The literature was scrutinized to discover the role of the lymphatic and venous systems in tumor metastasis and how microbes affect these processes. Some bacteria have a potent ability to enhance epithelial–mesenchymal transition, a critical step in the metastatic cascade. Bacteria also can modify the microenvironment and the local immune profile at a metastatic site. Early targeted antibiotic therapy should be further investigated as a measure to prevent metastatic spread in the setting of bacterial infection.
6
Albini, Adriana, and József Tímár. "Genomics of metastatic progression." Clinical & Experimental Metastasis 27, no. 6 (2010): 453. http://dx.doi.org/10.1007/s10585-010-9348-6.
Full text
7
Visentin, Sarah, Mirela Sedić, Sandra Kraljević Pavelić, and Krešimir Pavelić. "Targeting Tumour Metastasis: The Emerging Role of Nanotechnology." Current Medicinal Chemistry 27, no. 8 (2020): 1367–81. http://dx.doi.org/10.2174/0929867326666181220095343.
Full textAbstract:
The metastatic process has still not been completely elucidated, probably due to insufficient knowledge of the underlying mechanisms. Here, we provide an overview of the current findings that shed light on specific molecular alterations associated with metastasis and present novel concepts in the treatment of the metastatic process. In particular, we discuss novel pharmacological approaches in the clinical setting that target metastatic progression. New insights into the process of metastasis allow optimisation and design of new treatment strategies, especially in view of the fact that metastatic cells share common features with stem cells. Nano- and micro-technologies are herein elaborated in details as a promising therapeutic concept in targeted drug delivery for metastatic cancer. Progression in the field could provide a more efficient way to tackle metastasis and thus bring about advancements in the treatment and management of patients with advanced cancer.
8
Rupp, Kevin, Andreas Lösch, Yanren Linda Hu, et al. "Modeling metastatic progression from cross-sectional cancer genomics data." Bioinformatics 40, Supplement_1 (2024): i140—i150. http://dx.doi.org/10.1093/bioinformatics/btae250.
Full textAbstract:
Abstract Motivation Metastasis formation is a hallmark of cancer lethality. Yet, metastases are generally unobservable during their early stages of dissemination and spread to distant organs. Genomic datasets of matched primary tumors and metastases may offer insights into the underpinnings and the dynamics of metastasis formation. Results We present metMHN, a cancer progression model designed to deduce the joint progression of primary tumors and metastases using cross-sectional cancer genomics data. The model elucidates the statistical dependencies among genomic events, the formation of metastasis, and the clinical emergence of both primary tumors and their metastatic counterparts. metMHN enables the chronological reconstruction of mutational sequences and facilitates estimation of the timing of metastatic seeding. In a study of nearly 5000 lung adenocarcinomas, metMHN pinpointed TP53 and EGFR as mediators of metastasis formation. Furthermore, the study revealed that post-seeding adaptation is predominantly influenced by frequent copy number alterations. Availability and implementation All datasets and code are available on GitHub at https://github.com/cbg-ethz/metMHN.
9
Mitra, Sumegha, Kartikeya Tiwari, Ram Podicheti, et al. "Transcriptome Profiling Reveals Matrisome Alteration as a Key Feature of Ovarian Cancer Progression." Cancers 11, no. 10 (2019): 1513. http://dx.doi.org/10.3390/cancers11101513.
Full textAbstract:
Background: Ovarian cancer is the most lethal gynecologic malignancy. There is a lack of comprehensive investigation of disease initiation and progression, including gene expression changes during early metastatic colonization. Methods: RNA-sequencing (RNA-seq) was done with matched primary tumors and fallopian tubes (n = 8 pairs) as well as matched metastatic and primary tumors (n = 11 pairs) from ovarian cancer patients. Since these are end point analyses, it was combined with RNA-seq using high-grade serous ovarian cancer cells seeded on an organotypic three-dimensional (3D) culture model of the omentum, mimicking early metastasis. This comprehensive approach revealed key changes in gene expression occurring in ovarian cancer initiation and metastasis, including early metastatic colonization. Results: 2987 genes were significantly deregulated in primary tumors compared to fallopian tubes, 845 genes were differentially expressed in metastasis compared to primary tumors and 304 genes were common to both. An assessment of patient metastasis and 3D omental culture model of early metastatic colonization revealed 144 common genes that were altered during early colonization and remain deregulated even in the fully developed metastasis. Deregulation of the matrisome was a key process in early and late metastasis. Conclusion: These findings will help in understanding the key pathways involved in ovarian cancer progression and eventually targeting those pathways for therapeutic interventions.
10
Eckhardt, Bedrich L., Belinda S. Parker, Ryan K. van Laar, et al. "Genomic Analysis of a Spontaneous Model of Breast Cancer Metastasis to Bone Reveals a Role for the Extracellular Matrix." Molecular Cancer Research 3, no. 1 (2005): 1–13. http://dx.doi.org/10.1158/1541-7786.1.3.1.
Full textAbstract:
Abstract A clinically relevant model of spontaneous breast cancer metastasis to multiple sites, including bone, was characterized and used to identify genes involved in metastatic progression. The metastatic potential of several genetically related tumor lines was assayed using a novel real-time quantitative RT-PCR assay of tumor burden. Based on this assay, the tumor lines were categorized as nonmetastatic (67NR), weakly metastatic to lymph node (168FARN) or lung (66cl4), or highly metastatic to lymph node, lung, and bone (4T1.2 and 4T1.13). In vitro assays that mimic stages of metastasis showed that highly metastatic tumors lines were more adhesive, invasive, and migratory than the less metastatic lines. To identify metastasis-related genes in this model, each metastatic tumor was array profiled against the nonmetastatic 67NR using 15,000 mouse cDNA arrays. A significant proportion of genes relating to the extracellular matrix had elevated expression in highly metastatic tumors. The role of one of these genes, POEM, was further investigated in the model. In situ hybridization showed that POEM expression was specific to the tumor epithelium of highly metastatic tumors. Decreased POEM expression in 4T1.2 tumors significantly inhibited spontaneous metastasis to the lung, bone, and kidney. Taken together, our data support a role for the extracellular matrix in metastatic progression and describe, for the first time, a role for POEM in this process.
11
Shiraishi, Kenshiro, Keiichiro Tada, Jiro Kawamori, Atsushi Fukuuchi, and Tsunehiro Nishi. "Disease progression of metastatic breast cancer by first relapse site after definitive radiotherapy." Journal of Clinical Oncology 33, no. 28_suppl (2015): 36. http://dx.doi.org/10.1200/jco.2015.33.28_suppl.36.
Full textAbstract:
36 Background: Bone metastasis as initial distant relapse is commonly considered to have better prognosis than other sites in metastatic breast cancer. To elucidate true clinical course of metastatic disease, it is essential that we prospectively manage patients since primary setting. Methods: Overall, 3,417 patients with breast cancer treated with mastectomy (n = 379, 11.1%) or breast-conserving surgery (n = 3,029, 88.6%) followed by definitive radiotherapy at two institutions in Center of Tokyo between 1980 and 2014 were included in the study. Information on all patients was prospectively collected and rigorously-controlled. Initial metastatic relapse sites included bone, brain, and other (mainly visceral). Intrinsic subtypes of tumor were classified as luminal A, luminal-human epidermal growth factor receptor 2 (HER2), luminal B, triple negative, and HER2 identified by routine immunohistochemistry and histological grade. Cumulative incidence rates of overall survival (OS) for each affected site after metastatic relapse were estimated according to Kaplan-Meier method. Results: Median follow-up time for living patients was 113 months. A total of 370 patients experienced metastatic progression as first relapse event. Median duration of OS after initial metastatic relapse was 69 month in all subtypes. No difference was seen in OS among five subtypes after initial bone or brain relapse. Meanwhile, OS of luminal subtypes after initial other-site relapse was better than that of triple negative and HER2 subtypes (P = .003). Notably, OS rates of bone and non-bone/brain metastasis groups as initial relapse site were almost identical (P= .626). Conclusions: We find no difference in mortality after metastatic relapse between bone and other site except for brain metastasis as initial relapse in breast cancer patients following definitive radiotherapy in our cohort without primary metastatic setting. Careful consideration is needed for initial distant relapse regardless of which site is involved. However, prognosis of metastatic breast cancer after definitive radiotherapy is favorable based on real world data, attributable mainly to improved systemic therapy and modern multidisciplinary approach.
12
Hu, Dandan, Gong Chen, Yaojun Zhang, and Minshan Chen. "Next generation sequencing reveals the phylogenetic relationship of multi-organ metastatic colon cancer and molecular determinants of metastasis." Journal of Clinical Oncology 38, no. 15_suppl (2020): e13502-e13502. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e13502.
Full textAbstract:
e13502 Background: The clinical manifestation of metastatic colorectal cancer (mCRC) varies from patient to patient, with the underlying genetic alterations and expression profiles deceptive. We aim to investigate the phylogenetic relationships of the multi-organ mCRC and the possible biomarkers of disease progression. Methods: Whole Extron Sequencing (WES) was performed in CRC and their matched multi-organ metastases from three patients with different clinical manifestations. Sciclone calculation between individual lesions illustrated the evolutionary origins of each metastatic sites. Genomic divergence between primary and metastatic sites were identified and their potential role in the metastatic process were annotated. Following the WES results, the significantly correlated genes were validated by immunohistochemistry. Results: The evolutionary tree showed that the distant metastasis could originated from either the primary colon cancer or the other metastatic site. Organotropism exists in both mCRC and protein levels in terms of APOB, and a number of driver mutations potentially decide the disease progression. Moreover, the expressive change of APOB between primary CRC and CRC liver metastasis indicates worse long-term outcomes. Conclusions: Metastatic routes of multi-organ mCRC are highly heterogeneous. We identified previously unreported gene alterations might facilitate metastatic and organotropic progression, providing potential biomarkers for diagnosis and treatment.
13
Chen, Jocelyn F., and Qin Yan. "The roles of epigenetics in cancer progression and metastasis." Biochemical Journal 478, no. 17 (2021): 3373–93. http://dx.doi.org/10.1042/bcj20210084.
Full textAbstract:
Cancer metastasis remains a major clinical challenge for cancer treatment. It is therefore crucial to understand how cancer cells establish and maintain their metastatic traits. However, metastasis-specific genetic mutations have not been identified in most exome or genome sequencing studies. Emerging evidence suggests that key steps of metastasis are controlled by reversible epigenetic mechanisms, which can be targeted to prevent and treat the metastatic disease. A variety of epigenetic mechanisms were identified to regulate metastasis, including the well-studied DNA methylation and histone modifications. In the past few years, large scale chromatin structure alterations including reprogramming of the enhancers and chromatin accessibility to the transcription factors were shown to be potential driving force of cancer metastasis. To dissect the molecular mechanisms and functional output of these epigenetic changes, it is critical to use advanced techniques and alternative animal models for interdisciplinary and translational research on this topic. Here we summarize our current understanding of epigenetic aberrations in cancer progression and metastasis, and their implications in developing new effective metastasis-specific therapies.
14
Gerbec, Zachary J., Antonio Serapio-Palacios, Sarah E. Woodword, Jorge Pena Diaz, Brett Finlay, and Shoukat Dedhar. "Abstract A047: Tumor-derived bacteria drive breast cancer metastasis." Cancer Research 83, no. 2_Supplement_2 (2023): A047. http://dx.doi.org/10.1158/1538-7445.metastasis22-a047.
Full textAbstract:
Abstract Metastasis is a major barrier to long-term survival and therapeutic options for aggressive, metastatic forms of breast cancer remain limited. Studies using patient samples have identified tumor-resident bacteria that preferentially associate with specific breast cancer types including highly aggressive TNBC. However, it is not yet understood how intratumoral bacteria directly contributes to disease progression and metastatic propensity independent of other prognostic factors. It is therefore the goal of the Dedhar and Finlay labs to identify how specific bacteria within metastatic breast cancer control immune and tumor cell functions to regulate metastatic potential and determine the outcome of disease progression. Using the syngenic, immunocompetent 4T1 and 67NR breast cancer models of metastatic and non-metastatic disease, we found microbiome depletion significantly reduces primary tumor growth highly metastatic 4T1 tumors specifically. We also found bacterial depletion reduces metastatic burden and extends survival time compared to microbiome-replete controls. Along with alterations in disease progression, microbiome depletion induces changes in immune cell function that occur specifically in the metastatic 4T1 tumors, revealing differential microbial-based regulation of metastatic versus non-metastatic disease. To identify bacteria that control metastasis in microbiome-replete controls, we plated surgically resected tumor suspensions on bacterial growth media and compared bacteria from the 4T1 and 67NR primary tumors. We identified several species of the Bacillus genus that were unique to 4T1 tumors and were present both within the primary tumor as well as metastatic nodules. To determine how these bacteria effect disease progression, we designed several in vivo model systems to directly test the ability of the isolated bacteria to promote metastasis. Using an orthotopic inoculation model with 4T1 or EMT6 cells, we found that following intratumoral injection, the 4T1- derived Bacillus species was actually able to augment metastasis when introduced directly back into primary tumors. To determine the specificity of this phenomenon, we then compared the effects of the 4T1 and 67NR-isolated bacteria on metastasis by injecting 4T1 cells that had been co-cultured with either bacteria prior to injection. Interestingly, we found that while the 67NR-derived bacteria had little effect on metastasis, the 4T1-derived Bacillus species significantly enhanced metastatic tumor burden compared to all other groups including those cultured with the 67NR-derived bacteria. These data demonstrate the ability of certain bacteria to promote metastatic disease. Based on these findings, we hypothesize specific bacteria play a causative role in augmenting metastatic propensity, and seek to determine functional differences between intratumoral bacteria to identify mechanistic targets for prevention of metastasis. We also seek to expand this work into clinical models to identify potential prognostic factors as well as mechanistic targets for disease treatment. Citation Format: Zachary J. Gerbec, Antonio Serapio-Palacios, Sarah E. Woodword, Jorge Pena Diaz, Brett Finlay, Shoukat Dedhar. Tumor-derived bacteria drive breast cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference: Cancer Metastasis; 2022 Nov 14-17; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_2):Abstract nr A047.
15
Entwistle, Susannah, Hannah K. Jackson, Ian Kerr, Beth Coyle, and Alistair Hume. "MEDB-64. Are Rab GTPases metastatic drivers in metastatic medulloblastoma?" Neuro-Oncology 24, Supplement_1 (2022): i121. http://dx.doi.org/10.1093/neuonc/noac079.438.
Full textAbstract:
Abstract Medulloblastoma is the most common malignant paediatric brain cancer with poorer prognosis related to the onset of metastasis. It has four molecular subgroups; Wingless (WNT), Sonic Hedgehog (SHH), group 3 and group 4, of which group 3 is the most likely to be metastatic and is therefore associated with the poorest prognosis. Exosomes are small membrane-bound extracellular vesicles of endosomal origin which contain a variety of cargo including RNA and proteins. Increased exosome release is connected with disease progression and metastasis in multiple cancers. Rabs are a family of small GTPases (70 in humans) which regulate vesicle trafficking. Several Rabs are known to regulate exosome biogenesis and secretion and may thereby contribute to cancer progression. The role of Rabs in metastatic medulloblastoma is unclear. We aim to explore whether Rabs contribute to the progression of metastatic medulloblastoma through the exosome biogenesis and secretion pathways. Through analysis of literature, databases such as ExoCarta.org, the R2: Genomics analysis and visualisation platform, and mRNA content of medulloblastoma exosomes, five novel Rab candidates were identified that may contribute to disease progression in group 3 medulloblastoma. Gene expression of these Rabs was then verified across SHH, group 3 and group 4 patient-derived cell lines using RT-qPCR, with candidate Rab expression confirmed in the three subgroups. Presence of Rab mRNA has also been found in exosomes derived from group 3 and group 4 patients, with an enrichment in group 3 exosomes. Current and future work aims to determine the potential roles of Rabs in medulloblastoma pathogenesis, and to determine whether Rabs contribute to increased exosome biogenesis which drives metastasis or are metastatic drivers in medulloblastoma themselves. Therefore, experiments to characterise Rab candidate protein expression within cells and assess their function after knockdown are necessary and timely.
16
Stephenson, Andrew J., Michael W. Kattan, James A. Eastham, et al. "Defining Biochemical Recurrence of Prostate Cancer After Radical Prostatectomy: A Proposal for a Standardized Definition." Journal of Clinical Oncology 24, no. 24 (2006): 3973–78. http://dx.doi.org/10.1200/jco.2005.04.0756.
Full textAbstract:
Purpose Prostate-specific antigen (PSA) defined biochemical recurrence (BCR) of prostate cancer is widely used for reporting the outcome of radical prostatectomy (RP). A standardized BCR definition is lacking, and overall progression-free probability and risk of subsequent metastatic disease progression may vary greatly depending on the PSA criterion used. Ten definitions of BCR were evaluated to identify the one that best explains metastatic progression. Methods Of 3,125 patients who underwent RP at our institution since 1985, 75 developed distant metastasis during a median follow-up of 49 months. To predict metastasis progression, we modeled the clinical information using multivariable Cox regression analysis. BCR was included in the model as a time-dependent covariate, and separate models were developed for each definition. A goodness-of-fit (R2) statistic was used to determine the Cox model (and thereby the BCR definition) that best explained metastatic progression. Results The 10-year progression-free probability ranged from 63% to 79%, depending on the BCR definition. The model containing BCR defined as a PSA of at least 0.4 ng/mL followed by another increase best explained metastatic progression (R2 = 0.21). This definition was also associated with a high probability of subsequent secondary therapy, continued PSA progression, and rapid PSA doubling time. Conclusion BCR defined as a PSA value of at least 0.4 ng/mL followed by another increase best explains the development of distant metastasis among 10 candidate definitions, after controlling for clinical variables and the use of secondary therapy. On the basis of this evidence, we propose that this definition be adopted as the standard for reporting the outcome of RP.
17
Dilmac, Sayra, Nilay Kuscu, Ayse Caner, et al. "SIRT1/FOXO Signaling Pathway in Breast Cancer Progression and Metastasis." International Journal of Molecular Sciences 23, no. 18 (2022): 10227. http://dx.doi.org/10.3390/ijms231810227.
Full textAbstract:
Breast cancer is the second most common cancer in women. The roles of the SIRT and FoxO proteins in tumor progression are known, but their roles in metastasis have not yet been clearly elucidated. In our study, we investigated the roles of SIRT and FoxO proteins their downstream pathways, proteins p21 and p53, in tumor progression and metastasis. We evaluated these proteins in vitro using metastatic 4TLM and 67NR cell lines, as well as their expression levels in tumor-bearing mice. In addition, the regulatory role of SIRT and FoxO proteins in different transduction cascades was examined by IPA core analysis, and clinicopathological evidence was investigated in the TCGA database. In primary tumors, the expression levels of SIRT1, p21, p53, E2F1 and FoxO proteins were higher in 67NR groups. In metastatic tissues, the expression levels of SIRT1, E2F1 and FoxO proteins were found to be enhanced, whereas the levels of p53 and p21 expression were noted to be reduced. IPA analysis also provided empirical evidence of the mechanistic involvement of SIRT and FoxO proteins in tumor progression and metastasis. In conclusion, SIRT1 was found to co-operate with FoxO proteins and to play a critical role in metastasis. Additional research is required to determine why overexpression of SIRT1 in metastatic tissues has oncogenic effects.
18
Hovens, Christopher, Matthew Hong, Geoff Macintyre, et al. "Tracking clonal diversity in metastatic prostate cancer progression." Journal of Clinical Oncology 33, no. 7_suppl (2015): 193. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.193.
Full textAbstract:
193 Background: Genomic heterogeneity has been observed in a number of tumor types including prostate cancer. However, how subclonal tumor diversity changes during metastasis and progression to lethality remains unexplored. Large scale genomic analyses have reported the most prevalent somatic aberrations associated with the dominant clone of the tumor without permitting an analysis of subclonal complexity or how this complexity impinges on metastatic potential or resistance to treatment. Methods: To understand and track the evolution of lethal prostate cancer from initial therapy to end stage metastases, we performed longitudinal and multiregional sampling of tumors from 7 patients with lethal prostate cancer. We performed whole-genome sequencing, RNA sequencing, and SNP profiling. Computational approaches were used to reconstruct the genetic relationships and evolution of the tumors. These evolutionary tree reconstructions allowed us to observe the dynamics of chromoplexy and mutational processes along specific branches of tumor evolution. To refine the genetic landscape and spatial connections between subclones, we employed deep, targeted re-sequencing of variant loci in the original sequenced samples, in additional FFPE sites sampled from the organ confined tumors, and from blood. Results: We show that while all primary and metastatic prostate tumors share a single ancestral clone, metastases arise from subclones present at minor frequencies in the primary tumor. We reveal that individual metastases comprise mixtures of subclones indicative of intra-metastatic heterogeneity. We provide evidence for cross-metastatic site seeding and dynamic remolding of subclonal mixtures in response to therapy suggesting a distinct metastatic hierarchy. Ultra-deep sequencing of end-stage blood reveals the presence of diverse subclones with metastatic potential derived from various stages in the evolution of the tumor. Conclusions: Our results demonstrate unexpected complexity in the origins of both primary and metastatic prostate cancer, with distinct implications for treatment of advanced disease.
19
Karlow, Jennifer A., Siddhartha Devarakonda, Xiaoyun Xing, et al. "Developmental Pathways Are Epigenetically Reprogrammed during Lung Cancer Brain Metastasis." Cancer Research 82, no. 15 (2022): 2692–703. http://dx.doi.org/10.1158/0008-5472.can-21-4160.
Full textAbstract:
Abstract Non–small cell lung cancer (NSCLC) is one of the most commonly diagnosed and deadliest cancers worldwide, with roughly half of all patients initially presenting with both primary and metastatic disease. While the major events in the metastatic cascade have been identified, a mechanistic understanding of how NSCLC routinely and successfully colonizes the brain is largely unknown. Recent studies have begun demonstrating the role of epigenetic misregulation during tumorigenesis and metastasis, including widespread changes in DNA methylation and histone modifications. To better understand the role of altered DNA methylation in NSCLC metastasis to the brain, we measured DNA methylation during disease progression for 12 patients, globally profiling the methylation status of normal lung, primary lung tumor, and brain metastasis samples. The variation in methylation was similar during metastatic spread and primary tumorigenesis but less coordinated across genomic features during metastasis. The greatest recurrent changes during metastatic progression were methylation gains in DNA methylation valleys (DMV) harboring the constitutive heterochromatin mark H3K9me3 as well as bivalent marks H3K27me3 and H3K4me1. In a lymph node–derived cancer cell line, EZH2 binding within DMVs was lost, accompanied by an increase in DNA methylation, exemplifying epigenetic switching. The vast majority of the differentially methylated region–associated DMVs harbored developmental genes, suggesting that altered epigenetic regulation of developmentally important genes may confer a selective advantage during metastatic progression. The characterization of epigenetic changes during NSCLC brain metastasis identified recurrent methylation patterns that may be prognostic biomarkers and contributors to disease progression. Significance: Altered DNA methylation in lung cancer brain metastases corresponds with loss of EZH2 occupancy at developmental genes, which could promote stem-like phenotypes permissive of dissemination and survival in different microenvironments.
20
Green, Foad H., Matthew J. Rioth, and Joshua Loving. "Sequential learning for pan-tumor detection of metastatic disease progression." Journal of Clinical Oncology 41, no. 16_suppl (2023): e13591-e13591. http://dx.doi.org/10.1200/jco.2023.41.16_suppl.e13591.
Full textAbstract:
e13591 Background: Detection of progression of patients with early stage cancer is a challenge for real world data from electronic health records (EHR). Temporal patterns common to patients’ data can detect patients with metastatic progression. A deep learning approach on longitudinal patient records of cancer lab testing, visit diagnosis codes, and cancer treatments was used to identify metastatic status. Methods: ICD-10-CM diagnosis codes, clinical lab values specific to cancer testing, and antineoplastic treatments were evaluated from longitudinal data of 128,614 patients who did not progress and 5,884 who did develop metastasis, across 47 tumor types in the Syapse Learning Health Network. Patients metastatic at diagnosis were excluded. Data were included beginning at the time of primary cancer diagnosis and ended for all surviving patients at an established administrative cutoff date. In the metastatic group, visits after the progression event were included but censored if they contained diagnosis codes specifically for secondary malignant neoplasms. A binary classification was developed using a multi-headed attention transformer in order to determine metastatic status. Patient history was sequentially aggregated to visit-level embeddings across their longitudinal record. Categorical layers were used for antineoplastics and diagnosis codes. Linear layers were used to embed lab values, as well as for visit intervals from primary cancer date and administrative cutoff date. All embeddings were used as feature inputs for the classifier. Pre-training random sampling of the non-metastatic population was applied to establish equally-weighted labels in a 80:10:10 split for training, validation, and testing sets; to account for the smaller population of patients who progressed to metastatic status. Results: This classification approach achieved 0.86 PR-AUC, 0.79 ROC-AUC, and 0.75 F1. This performance is comparable to published models trained for single tumor cohort prediction. With our censoring constraints, these model results are robust in the absence of routine signals of metastasis in the EHR, such as staging reports and diagnosis coding for distant metastases. Conclusions: This method generalizes, across multiple cancer types, an accurate classification of metastatic progression from patient visit history. This work is immediately useful for real world evidence data analysis complementing patients with metastases already captured in hospital registries. Using sequential deep learning with EHR data classes, this approach may be used to forecast metastatic progression for early intervention.
21
Oliveira, Renata Ramalho, Douglas V. Faget, Xianmin Luo, Jiayu Ye, Joseph B. Monahan, and Sheila A. Stewart. "Abstract 244: Limiting metastatic breast cancer progression by targeting MK2 stromal signaling." Cancer Research 82, no. 12_Supplement (2022): 244. http://dx.doi.org/10.1158/1538-7445.am2022-244.
Full textAbstract:
Abstract Breast cancer is now the most common cancer among women in the US and metastasis to distant organs is the major cause of death in these patients. Among metastatic sites, bone is the most frequent destination of breast cancer metastasis and once the disease is found in the bone, it is often refractory to standard therapy. In addition, bone metastasis is associated with significant skeletal related events that greatly impact quality of life. Thus, there is a significant need to develop novel therapies that extend survival and improve quality of life. Previously we found that MK2 inhibition (MK2i) limits metastatic growth by targeting the tumor stromal compartment. To determine which stromal cells are targeted by MK2i we isolated stromal cells from within a metastatic bone lesion and carried out single cell RNA sequencing (scRNA-Seq). Using this approach, we found numerous gene expression changes in both the immune (CD45+) and non-immune (CD45-) populations upon MK2i. Indeed, we found significant numbers of p16+ senescent fibroblasts were present inside the metastatic lesion. We also found vascular cancer-associated fibroblasts (vCAF) and matrix CAFs (mCAF) inside the metastatic lesion suggesting that CAFs are not limited to primary disease. Numerous changes in gene expression in CD45+ cells were also observed, and these changes are being used to identify viable immunotherapies to deploy in our model. Finally, we are using conditional MK2 mice to establish the cell type targeted by MK2i. Our data demonstrate that MK2i is as effective as chemotherapy at limiting metastatic progression and our approach to leverage the scRNA-Seq data may allow us to optimize MK2i therapy to improve patient outcomes and quality of life. Citation Format: Renata Ramalho Oliveira, Douglas V. Faget, Xianmin Luo, Jiayu Ye, Joseph B. Monahan, Sheila A. Stewart. Limiting metastatic breast cancer progression by targeting MK2 stromal signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 244.
22
Zarrella, Mark, Joon Kyoo Lee MD, and Sang-Chul Lim. "R412 – Role of KITENIN in Progression and Metastasis of SCC." Otolaryngology–Head and Neck Surgery 139, no. 2_suppl (2008): P181. http://dx.doi.org/10.1016/j.otohns.2008.05.566.
Full textAbstract:
Problem The expression of KAI1 (a metastatic suppressor gene) in cancer cells results in reduced cell motility and invasiveness. A cDNA clone of VANGL1, a member of the tetraspanin protein family that specifically interacts with the COOH-terminal cytoplasm domain of KAI1, was isolated and renamed KITENIN (KAI1 COOH-terminal interacting tetraspanin). The purpose of this study was to investigate the role of KITENIN on the progression and metastasis of transfected squamous cell carcinoma using in vivo and in vitro experiments. Methods Locally advanced squamous cell carcinoma tissues from five patients were obtained for investigation of KITENIN expression. Malignant tumors, normal adjacent mucosa tissues, metastatic lymph nodes, and non-metastatic lymph nodes were collected. KITENIN or vector only (control) was transfected into SCC (squamous cell carcinoma) VII, a mouse squamous cell carcinoma cell line, using FuGENE 6. An in vitro assay (invasion, migration, and proliferation) for KITENIN and the vector-transfected group was studied. The KITENIN or vector-transfected SCC VII cells were injected subcutaneously into 12 C3H/HeJ syngeneic mice (6 mice for each group). The tumor size was measured daily for 4 weeks. During the fifth week after injection, the presence of metastasis in the lung and liver tissue was evaluated for each mouse with a tumor mass on the back; the tissues were assessed by gross and microscopic examination. Results KITENIN was highly expressed in tumors and metastatic lymph nodes from patients. KITENIN-transfected cells showed significantly increased invasion, migration, and proliferation compared with the vector-transfected cells. Tumor volume was more increased in the KITENIN-transfected cells-injected mice. Lung metastasis was found in the KITENIN-group (3/6 mice), while no metastasis in the vector-group. Conclusion KITENIN participates in the progression and metastasis of SCC. Significance An antisense KITENIN strategy may be a useful method to inhibit progression and metastasis in squamous cell carcinoma. Support This study was financially supported by Chonnam National University, 2006.
23
Nestler, Tim, Priya Dalvi, Friederike Haidl, et al. "Transcriptome analysis reveals upregulation of immune response pathways at the invasive tumour front of metastatic seminoma germ cell tumours." British Journal of Cancer 126, no. 6 (2022): 937–47. http://dx.doi.org/10.1038/s41416-021-01621-5.
Full textAbstract:
Abstract Background Testicular germ cell tumours (TGCTs) have a high metastasis rate. However, the mechanisms related to their invasion, progression and metastasis are unclear. Therefore, we investigated gene expression changes that might be linked to metastasis in seminomatous testicular germ cell tumour (STGCT) patients. Methods Defined areas [invasive tumour front (TF) and tumour centre (TC)] of non-metastatic (with surveillance and recurrence-free follow-up >2 years) and metastatic STGCTs were collected separately using laser capture microdissection. The expression of 760 genes related to tumour progression and metastasis was analysed using nCounter technology and validated with quantitative real-time PCR and enzyme-linked immunosorbent assay. Results Distinct gene expression patterns were observed in metastatic and non-metastatic seminomas with respect to both the TF and TC. Comprehensive pathway analysis showed enrichment of genes related to tumour functions such as inflammation, angiogenesis and metabolism at the TF compared to the TC. Remarkably, prominent inflammatory and cancer-related pathways, such as interleukin-6 (IL-6) signalling, integrin signalling and nuclear factor-κB signalling, were significantly upregulated in the TF of metastatic vs non-metastatic tumours. Conclusions IL-6 signalling was the most significantly upregulated pathway in metastatic vs non-metastatic tumours and therefore could constitute a therapeutic target for future personalised therapy. In addition, this is the first study showing intra- and inter-tumour heterogeneity in STGCT.
24
Audouin, Marie, Géraldine Cancel Tassin, Cécile Gaffory, et al. "Association of Rs1139971, a KAI1 polymorphism, with bone metastasis progression in prostate cancer and ganglionnary metastasis." Journal of Clinical Oncology 31, no. 15_suppl (2013): e16089-e16089. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.e16089.
Full textAbstract:
e16089 Background: Metastatic prostate cancer, with bones as principal location, is responsible for most of the death from this malignancy. If the molecular mecanisms of the metastasis progression are not completely solved, many involved pathways have been clarified. Association studies have proven that genetic factors could affect the risk of prostate cancer or its agressiveness. Likewise, some polymorphisms from genes involved in metastatic pathways could have a meaningfull function in the individual genetic susceptibility to metastatic prostate cancer. The KAI1 gene is known to be implicated in the metastatic process of many malignant tumors, such as breast, lung or colorectal cancer. Moreover, the protein encoded by this gene seems to act as a metastatic suppressor. In this study, we searched for an association between the risk of metastatic progression and a polymorphism from the KAI gene (rs1139971). Methods: It was a retrospective and multicentrique study, comparing 195 patients harbouring bone and/or ganglionnary metastatic prostate cancer with 386 patients affected by a non metastatic prostate cancer. All the patients were caucasians. The variant rs1139971 has been genotyped by Taqman technology. Results: The allele A from rs1139971 was found to be less frequent in metastatic patients but this result wasn’t significant. The patients were then stratified according to the metastatic location : bone or ganglionnary. In this case, the allele A was significantly associated with metastatic risk in the group of patients with bone metastasis [OR = 0,525 ; IC 95% = 0,332-0,828 ; p = 0,0056]. Conclusions: In this study, a significant association has been pointed up between bone metastatic prostate cancer and the polymorphism rs1139971 from KAI1 gene. However, these results need to be confirmed on a larger and independant population.
25
McDonald, Erica, Sierra Cheng, Vanessa S. Arciero, et al. "Prevalence of oligoprogressive, metastatic castration-resistant prostate cancer (mCRPC) amenable to stereotactic ablative radiotherapy (SABR) in men undergoing abiraterone acetate (AA) therapy." Journal of Clinical Oncology 35, no. 6_suppl (2017): e587-e587. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.e587.
Full textAbstract:
e587 Background: SABR is increasingly used for the treatment of men with oligometastatic prostate cancer, including patients (pts) presenting with oligoprogression. The latter is a clinical situation where a limited number of metastatic tumor sites progress (usually defined as ≤ 3-5), while all other metastases are controlled by a given systemic therapy. The frequency of oligoprogression potentially amenable to SABR is unknown. Methods: Thus, in a retrospective chart analysis we studied the progression pattern of 35 men with chemotherapy-naïve mCRPC undergoing AA therapy, and of 20 men undergoing AA therapy after docetaxel chemotherapy. Applying RECIST1.1 and/or PCWG2 criteria, pts were considered SABR candidates if they radiologically progressed in ≤ 5 distinct metastatic locations, while all other metastases were stable or responding. Results: In chemotherapy-naïve men, pre-AA metastatic lesions were located in bone (94%), lymph nodes (49%), lungs (17%) and liver (3%), whereas progression during AA therapy occurred in bone (89%), lymph nodes (49%), lungs (14%) and liver (9%). 12 pts (34%) fulfilled the criteria of oligoprogression with a median of 2 progressive lesions/pt (range 1-5). 8 pts presented with bone progression only, 3 with nodal progression, and 1 pt with combined bone/nodal progression. Post-docetaxel pts had pre-AA metastatic lesions located in bone (75%), lymph nodes (35%), lungs (5%) and liver (5%). Progression during AA therapy occurred in bone (80%), lymph nodes (75%), lungs (20%) and liver (5%). Only 1 pt met oligoprogression criteria with a single progressive bone metastasis. Conclusions: A sizeable number of men with chemotherapy-naïve mCRPC progressing during AA therapy might be considered for SABR. By contrast, progression of post-docetaxel mCRPC treated with AA is typically widespread. Further efforts are needed to identify criteria for oligoprogressive pts most suitable for SABR with sustained benefit versus men that may progress rapidly with widespread metastases following radiotherapy.
26
McDonald, Erica, Sierra Cheng, Vanessa Sarah Arciero, et al. "Prevalence of oligoprogressive, metastatic castration-resistant prostate cancer (mCRPC) amenable to stereotactic ablative radiotherapy (SABR) in men undergoing abiraterone acetate (AA) therapy." Journal of Clinical Oncology 35, no. 15_suppl (2017): e16509-e16509. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e16509.
Full textAbstract:
e16509 Background: SABR is increasingly used for treating men with oligometastatic prostate cancer, a state between loco-regional and widespread metastatic disease that exists de novo, presents as oligorecurrence, is treatment-induced, or occurs as oligoprogression. The latter is a clinical situation where a limited number of metastatic tumor sites progress (usually defined as ≤3-5), while all other metastases are controlled by a given systemic therapy. The frequency of oligoprogression amenable to SABR is unknown. Methods: Thus, in a retrospective chart analysis we studied the progression pattern of 35 men with chemotherapy-naïve mCRPC undergoing AA therapy, and of 20 men undergoing AA therapy after docetaxel chemotherapy. Applying RECIST1.1 and/or PCWG2 criteria, patients (pts) were considered SABR candidates if they radiologically progressed in ≤5 distinct metastatic locations, while all other sites were stable or responding. Results: In chemotherapy-naïve men, pre-AA metastatic lesions were located in bone (94%), lymph nodes (49%), lungs (17%) and liver (3%), whereas progression during AA therapy occurred in bone (89%), lymph nodes (49%), lungs (14%) and liver (9%). 12 pts (34%) met the criteria of oligoprogression with a median of 2 progressive lesions/pt (range 1-5). 8 pts presented with bone progression only, 3 with nodal progression, and 1 pt with combined bone/nodal progression. Post-docetaxel pts had pre-AA metastatic lesions located in bone (75%), lymph nodes (35%), lungs (5%) and liver (5%). Progression during AA therapy occurred in bone (80%), lymph nodes (75%), lungs (20%) and liver (5%). Only 1 pt met oligoprogression criteria with a single progressive bone metastasis. Conclusions: A sizeable number of men with chemotherapy-naïve mCRPC progressing during AA therapy might be considered for SABR. By contrast, progression of post-docetaxel mCRPC treated with AA is typically widespread. Further efforts are needed to identify criteria for oligoprogressive pts most suitable for SABR with sustained benefit versus men that may progress rapidly with widespread metastases following radiotherapy.
27
Suh, Jeong Yoon, Se Jung Maeng, Mirinae Kim, Su Jeong Kang, Young Wook Choi, and In Ho Chang. "Current Trends in Liquid Biopsy Technology for Early Diagnosis of Metastatic Renal Cell Carcinoma." Korean Journal of Urological Oncology 20, no. 4 (2022): 223–34. http://dx.doi.org/10.22465/kjuo.2022.20.4.223.
Full textAbstract:
Clear cell renal cell carcinoma (ccRCC) is a disease with a wide variety of clinical progressions such as the rate of disease progression or the degree of metastasis. About 30% of ccRCC patients suffer from metastatic diseases, and about 30% develop metastasis after diagnosis. In the case of metastatic RCC, early prediction of the disease is important because of the poor prognosis, but ccRCC-specific molecular markers for clinical use are not available yet. As an alternative, liquid biopsy, which can find molecules released from tumor tissues in circulating blood and obtain information on metastatic dissemination and recurrence of ccRCC, is emerging. In this article, we will introduce molecules such as cell free DNA, cell free RNA, protein, and exosomes available as circulating biomarkers for liquid biopsy. We will also introduce some promising technologies that can compensate for the limitations of liquid biopsy.
28
Ajithkumar, Priyadarshana, Sai Shyam Vasantharajan, Sharon Pattison, John L. McCall, Euan J. Rodger, and Aniruddha Chatterjee. "Exploring Potential Epigenetic Biomarkers for Colorectal Cancer Metastasis." International Journal of Molecular Sciences 25, no. 2 (2024): 874. http://dx.doi.org/10.3390/ijms25020874.
Full textAbstract:
Metastatic progression is a complex, multistep process and the leading cause of cancer mortality. There is growing evidence that emphasises the significance of epigenetic modification, specifically DNA methylation and histone modifications, in influencing colorectal (CRC) metastasis. Epigenetic modifications influence the expression of genes involved in various cellular processes, including the pathways associated with metastasis. These modifications could contribute to metastatic progression by enhancing oncogenes and silencing tumour suppressor genes. Moreover, specific epigenetic alterations enable cancer cells to acquire invasive and metastatic characteristics by altering cell adhesion, migration, and invasion-related pathways. Exploring the involvement of DNA methylation and histone modification is crucial for identifying biomarkers that impact cancer prediction for metastasis in CRC. This review provides a summary of the potential epigenetic biomarkers associated with metastasis in CRC, particularly DNA methylation and histone modifications, and examines the pathways associated with these biomarkers.
29
Gründker, Carsten, Matthias Läsche, Johanna Hellinger, and Günter Emons. "Mechanisms of Metastasis and Cell Mobility – The Role of Metabolism." Geburtshilfe und Frauenheilkunde 79, no. 02 (2019): 184–88. http://dx.doi.org/10.1055/a-0805-9113.
Full textAbstract:
AbstractTumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.
30
Bodogai, Monica, Purevdorj Olkhanud, Yrina Rochman, et al. "Thymic stromal lymphopoietin mediates breast cancer progression and metastasis (48.9)." Journal of Immunology 186, no. 1_Supplement (2011): 48.9. http://dx.doi.org/10.4049/jimmunol.186.supp.48.9.
Full textAbstract:
Abstract Breast cancer escape and metastasis is an active process that requires inflammation and participation of immune cells. We have previously reported that this is a primary tumor-controlled process which activates lungs to produce CCL17 and CCL22 to facilitate lung metastasis together with the recruitment of CCR4+ regulatory T cells (Tregs). To understand the mechanism of this process, we performed expression array analysis in both metastatic and non-metastatic cancer cells and found that metastatic cells produced thymic stromal lymphopoietin (TSLP), an IL-7-like type 1 inflammatory cytokine that is often associated with the induction of Th2-type allergic responses in the lungs. Moreover, TSLP was also abundantly expressed in variety of human solid tumors, including breast, lung, colon and ovarian cancers. To gain further insights into the role of TSLP in cancer progression, we have blocked TSLP expression in cancer cells and found that TSLP is required for efficient breast cancer escape and metastasis. Moreover, utilizing adoptive transfer studies in TSLPR deficient mice, we demonstrated that by targeting CD4+ T cells to induce Th2-type inflammatory responses, cancer-produced TSLP promoted cancer escape. Taken together, our data indicate that TSLP is an important factor that needs to be controlled to effectively combat with cancer escape.
31
Knuutila, Jaakko S., Pilvi Riihilä, Liisa Nissinen, Roosa Kallionpää, Teijo Pellinen, and Veli-Matti Kähäri. "Abstract 2101: Cancer-associated fibroblast activation predicts progression, metastasis, and prognosis of cutaneous squamous cell carcinoma." Cancer Research 83, no. 7_Supplement (2023): 2101. http://dx.doi.org/10.1158/1538-7445.am2023-2101.
Full textAbstract:
Abstract Purpose: Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer and the metastatic disease is associated with poor prognosis. At present, no established biomarkers are available for predicting the metastasis risk and prognosis of patients with cSCC. Cancer-associated fibroblasts (CAFs) promote the progression of cancer, but their role in cSCC is largely unknown. Here, we have examined the potential of CAF markers in the assessment of metastasis risk and prognosis of primary cSCC. Experimental Design: We utilized multiplexed fluorescence immunohistochemistry for profiling of CAF landscape in metastatic and non-metastatic primary human cSCCs, the actual metastases, and in premalignant and benign epidermal lesions. Quantitative high-resolution image analysis was performed with two separate panels of antibodies for CAF markers and the results were correlated with clinical and histopathological parameters including disease-specific mortality. Results: Increased stromal expression of fibroblast activation protein (FAP), α-smooth muscle actin, and secreted protein acidic and rich in cysteine (SPARC) were associated with progression of premalignant epidermal lesions to invasive cSCC. Furthermore, elevation of FAP and platelet-derived growth factor receptor-β (PDGFRβ) expression was associated with the risk of metastasis of primary cSCCs. High expression of PDGFRβ and periostin correlated with poor prognosis. Furthermore, a multi-marker defined CAF subset, PDGFRα-/PDGFRβ+/FAP+, was associated with invasion and metastasis and independently predicted poor disease-specific survival. Conclusions: These results show, that fibroblast activation evolves during the progression of cSCC. High PDGFRβ expression alone and multimarker combination PDGFRα-/PDGFRβ+/FAP+ are potential biomarkers for the progression of primary cSCC to metastatic stage, and for poor prognosis. Citation Format: Jaakko S. Knuutila, Pilvi Riihilä, Liisa Nissinen, Roosa Kallionpää, Teijo Pellinen, Veli-Matti Kähäri. Cancer-associated fibroblast activation predicts progression, metastasis, and prognosis of cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2101.
32
Lin, Siyue, Soonbum Park, Alexander Chui, et al. "Abstract 3932: Elucidating mechanisms of metastatic progression in bladder cancer with novel GEMMs and systems biology approaches." Cancer Research 85, no. 8_Supplement_1 (2025): 3932. https://doi.org/10.1158/1538-7445.am2025-3932.
Full textAbstract:
Abstract Metastasis is the leading cause of bladder cancer deaths. Despite recent advances in treatment, metastatic bladder cancer remains incurable. One of the major challenges in studying metastasis has been the lack of suitable in vivo models that recapitulate the natural evolution of metastatic progression within the native tumor microenvironment. To address this, we have generated genetically-engineered mouse models (GEMMs) of bladder cancer that have highly penetrant metastatic phenotypes. In particular, our new metastatic GEMMs build on our previously established GEMM, in which bladder-specific co-inactivation of Pten and p53 (double knockout, DKO), leads to muscle-invasive bladder cancer (MIBC) with a low incidence of metastasis. By introducing loss-of-function mutations in Arid1a, an epigenetic regulator that is frequently mutated in high-grade human bladder cancer, we generated triple knockout (TKO) mice. These mice develop highly lethal MIBC with over 80% incidence of regional and distant metastasis. Histopathological characterization of TKO tumors revealed aggressive features, including aberrant differentiation and enhanced invasiveness, and demonstrated strong conservation with human MIBC, as shown by the expression of basal and luminal subtype markers. We implemented a systems biology approach to identify mechanistic determinants, or master regulators (MRs), of metastasis. To identify drivers of metastatic progression, we first performed RNA sequencing to compare metastatic tumors with pre-tumor bladder urothelium from TKO mice. Gene signatures from TKO tumors were highly conserved with human MIBC. Cross-species analysis integrating TKO mouse data with human bladder cancer datasets identified conserved MRs predictive of adverse outcome in several independent patient cohorts. Key regulators of bladder cancer, such as Pparg and Shh, and lineage plasticity drivers, like Sox11, emerged as candidates. To prioritize these MRs, we performed CRISPR-based functional screening, which highlighted promising targets that are now being evaluated in our mouse models. In summary, we developed GEMMs that faithfully model metastatic bladder cancer. Our cross-species analysis identified a panel of conserved MRs, including Pparg, Shh, and Sox11, as key drivers of lineage plasticity and metastatic progression. These findings offer insights into the mechanisms of bladder cancer metastasis and suggest novel therapeutic opportunities. Citation Format: Siyue Lin, Soonbum Park, Alexander Chui, John R. Christin, Andrea Califano, Michael M. Shen, Cory Abate-Shen. Elucidating mechanisms of metastatic progression in bladder cancer with novel GEMMs and systems biology approaches [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3932.
33
Müller, Christian, Sabine Franke, Timo Reisländer, Verena Keitel, and Marino Venerito. "Sustained Clinical Response to Ivosidenib in Previously Treated Patients with Advanced Intrahepatic Cholangiocarcinoma Harboring an IDH1 R132 Mutation: Two Case Reports." Case Reports in Oncology 17, no. 1 (2024): 753–62. http://dx.doi.org/10.1159/000539665.
Full textAbstract:
Introduction: Patients with progressing intrahepatic cholangiocarcinoma (iCCA) harboring an isocitrate dehydrogenase 1 (IDH1) mutation who received ivosidenib showed a median progression-free survival (PFS) benefit of 1.3 months compared to placebo in the phase 3 ClarIDHy trial. Case Presentations: We describe 2 consecutive patients with previously treated unresectable and metastatic iCCA harboring an IDH1 R132 mutation who achieved durable clinical responses with ivosidenib 500 mg once daily for >12 months until disease progression. In one case with a mixed response, a single progressive liver metastasis was additionally treated locally with interstitial brachytherapy, while ivosidenib was continued until further progression. Ivosidenib therapy resulted in long-term disease control with PFS of 20 and 13 months and duration of treatment of 26 and 13 months, respectively, with no relevant side effects. Conclusion: Patients with unresectable or metastatic IDH1-mutated iCCA can achieve sustained clinical responses for >12 months with ivosidenib. No new safety signals were observed during long-term treatment with ivosidenib.
34
Westlake, Babe, Jeffrey Brown, Jacqueline Hart, Cameron Skiby, Kevin Jones, and John Groundland. "Exploring the Diagnostic Dilemma of Indeterminate Pulmonary Nodules in Patients with Primary Sarcoma of Bone." Sarcoma 2024 (March 5, 2024): 1–13. http://dx.doi.org/10.1155/2024/9926675.
Full textAbstract:
Introduction. Bone sarcomas are known to have a predilection for pulmonary metastasis. Surveillance protocols are thus focused on periodic chest imaging, typically with CT scan. Pulmonary nodules can be easily identified with this modality, but smaller nodules are not readily biopsied and may not represent metastatic disease. These are called indeterminate. The natural history of indeterminate nodules in a bone sarcoma population and factors associated with progression to true metastatic disease are not clearly defined. Methods. All bone sarcoma patients treated at a single institution from 2010 to 2020 were eligible for inclusion. We treated 327 patients over this period; 119 were excluded for age less than 16 years, 31 were excluded for evident metastatic disease at presentation, and 60 were excluded for incomplete clinical follow-up or CT chest imaging either at staging or in surveillance. We assessed chest CT images for presence of pulmonary nodules and selected variables both at the staging and on surveillance images. Nodules were considered metastatic if proven histologically with a biopsy or by clinical interpretation by the multidisciplinary sarcoma team. Clinical and imaging factors were assessed for the association of indeterminate nodule progression to true metastatic disease. Results. Seventy three of the 117 patients had indeterminate nodules on their staging CT scan; 41.1% of those patients progressed to metastatic disease compared to 43.2% of the patients that did not have indeterminate nodules on staging CT. Fifty eight of the 117 patients developed indeterminate nodules on surveillance chest CT, and 55.2% of those patients progressed to metastatic disease. There were no clinical or imaging factors that predicted the development of metastatic disease in the group that had indeterminate nodules at presentation; however, the number and size of nodules did correlate with progression to metastasis in those that developed indeterminate nodules on surveillance. Conclusion. Indeterminate pulmonary nodules are common on staging CT scans in patients with a bone sarcoma. The presence or absence of these indeterminate nodules was not predictive of progression to true metastatic disease in this cohort. However, the development of indeterminate nodules on surveillance imaging was associated with progression to metastatic disease with the size and number of nodules being important factors.
35
Bartoszyński, Robert. "On metastatic progression of cancer." Advances in Applied Probability 17, no. 2 (1985): 245–46. http://dx.doi.org/10.2307/1427131.
Full text
36
Bartoszyński, Robert. "On metastatic progression of cancer." Advances in Applied Probability 17, no. 02 (1985): 245–46. http://dx.doi.org/10.1017/s0001867800014877.
Full text
37
Rodolfo, Monica, Maria Daniotti, and Viviana Vallacchi. "Genetic progression of metastatic melanoma." Cancer Letters 214, no. 2 (2004): 133–47. http://dx.doi.org/10.1016/j.canlet.2004.06.049.
Full text
38
Usmani, B. A. "Genomic Instability and Metastatic Progression." Pathobiology 61, no. 2 (1993): 109–16. http://dx.doi.org/10.1159/000163771.
Full text
39
Tímár, József, and Andrea Ladányi. "Metastatic Progression of Human Melanoma." Cancers 15, no. 4 (2023): 1225. http://dx.doi.org/10.3390/cancers15041225.
Full textAbstract:
This Topical Collection, comprising 13 papers (10 original articles and 3 reviews), addresses various aspects of the field of melanoma progression: genomic and proteomic approaches, experimental studies, the questions of sentinel lymph node dissection, and metastasis formation of uveal and conjunctival melanomas is also discussed [...]
40
Askeland, Eric J., Vincent A. Chehval, Ryan W. Askeland, et al. "Cell cycle progression score to predict metastatic progression of clear cell renal cell carcinoma after resection." Journal of Clinical Oncology 32, no. 4_suppl (2014): 442. http://dx.doi.org/10.1200/jco.2014.32.4_suppl.442.
Full textAbstract:
442 Background: Clear cell renal cell carcinoma (ccRCC) is primarily treated surgically when organ confined, but requires close follow-up to evaluate for recurrence. Expression levels of cell cycle progression (CCP) genes have prognostic value in certain cancers. We evaluated the prognostic value of the CCP expression in surgically resected ccRCC. Methods: Medical records were retrospectively reviewed. Patients with metastasis or lymph node involvement at surgery were excluded. Cases developed metastasis within 5 years of resection; controls were followed for at least 4.5 years without recurrence. Specimens were re-reviewed by a single pathologist. Tumor FFPE slides were macrodissected and RNA extracted. CCP score, sex, age, T stage, Fuhrman Nuclear grade (FNG), tumor size, smoking status, lymphovascular invasion (LVI), and time to metastasis were available for analysis. Univariate and multivariate analyses were used to evaluate association with metastatic progression. Subsequently, the tumor transcriptome was interrogated for other informative biomarkers using next-generation sequencing (NGS). Funding was by Myriad Genetics. Results: Twenty-six cases and 38 controls were evaluated. Median time to metastasis was 1.68 years (IQR 1.06-3.69) for the case group. Median follow-up was 6.69 years for controls. Univariate analysis revealed that LVI (OR 4.64, p=0.005), FNG (OR 4.16, p=0.0099) and CCP score (OR 2.65, p=0.0091) were significantly associated with progression to metastasis. In multivariate analysis, age (p=0.026), tumor size (p=0.022) and CCP score (p=0.026) were statistically significant. A step-wise multivariate model including age, CCP, tumor size and LVI had an AUC of 0.84, which decreased to 0.78 if CCP score was excluded. CCP scores calculated by qPCR and NGS were correlated (rho = 0.91). However, no other genes showed a significant association with metastasis or TNM stage (after correcting for multiple testing) in univariate analysis or after adjusting for CCP score. Conclusions: The cell cycle progression score predicts metastatic progression after resection of ccRCC and appears to add significant prognostic information to standard clinical and pathological variables.
41
Biswas, Anup K., and Swarnali Acharyya. "Cancer-Associated Cachexia: A Systemic Consequence of Cancer Progression." Annual Review of Cancer Biology 4, no. 1 (2020): 391–411. http://dx.doi.org/10.1146/annurev-cancerbio-030419-033642.
Full textAbstract:
Cancer is a life-threatening disease that has plagued humans for centuries. The vast majority of cancer-related mortality results from metastasis. Indeed, the invasive growth of metastatic cancer cells in vital organs causes fatal organ dysfunction, but metastasis-related deaths also result from cachexia, a debilitating wasting syndrome characterized by an involuntary loss of skeletal muscle mass and function. In fact, about 80% of metastatic cancer patients suffer from cachexia, which often renders them too weak to tolerate standard doses of anticancer therapies and makes them susceptible to death from cardiac and respiratory failure. The goals of this review are to highlight important findings that help explain how cancer-induced systemic changes drive the development of cachexia and to discuss unmet challenges and potential therapeutic strategies targeting cachexia to improve the quality of life and survival of cancer patients.
42
Chousakos, Emmanouil, Daniela Zugna, Emi Dika, et al. "Topographical and Chronological Analysis of Thin Cutaneous Melanoma’s Progressions: A Multicentric Study." Cancers 15, no. 15 (2023): 3989. http://dx.doi.org/10.3390/cancers15153989.
Full textAbstract:
A great portion of cutaneous melanoma’s diagnoses nowadays is attributed to thin tumors with up to 1 mm in Breslow thickness (hereafter thin CMs), which occasionally metastasize. The objective of this study was to identify thin CM’s metastatic patterns from a topographical and chronological standpoint. A total of 204 cases of metastatic thin CMs from five specialized centers were included in the study, and corresponding data were collected (clinical, epidemiological, histopathological information of primary tumor and the number, anatomical site, and time intervals of their progressions). First progressions occurred locally, in regional lymph nodes, and in a distant site in 24%, 15% and 61% of cases, respectively, with a median time to first progression of 3.10 years (IQR: 1.09–5.24). The median elapsed time between the first and second progression and between the second and third progression was 0.82 (IQR: 0.34–1.97) and 0.49 (IQR: 0.21–2.30) years, respectively, while the median survival time was about 4 years since first progression. Furthermore, the sequences of locations and time intervals of the progressions were associated with the clinicopathological and demographic features of the primary tumors along with the features of the preceding progressions. In conclusion, the findings of this study describe the natural history of thin CMs, thus highlighting the necessity to identify subgroups of thin CMs at a higher risk for metastasis and contributing to the optimization of the management and follow-up of thin CM patients.
43
Park, Joo Un, and Jae Wan Jung. "Metastatic ameloblastoma with postoperative accelerated tumor growth treated with carboplatin and paclitaxel: a case report." Kosin Medical Journal 37, no. 1 (2022): 83–88. http://dx.doi.org/10.7180/kmj.21.030.
Full textAbstract:
Ameloblastoma is a histologically benign odontogenic epithelial tumor that rarely metastasizes. However, metastasis to the lungs can occur, usually years after the development of the primary tumor. Here, we present the case of a 63-year-old woman with metastatic ameloblastoma in the lungs that developed 12 years after surgery for the primary lesion. As is typical for metastatic ameloblastomas, the tumor was incidentally found on radiography and surgically removed. However, the tumor exhibited accelerated progression with pleural metastasis after surgical removal, which is unusual in metastatic ameloblastoma. The patient was successfully treated with carboplatin/paclitaxel and showed a partial response to tumor progression, implying that this approach can be safely used in the absence of a standard treatment regimen.
44
Park, Jin Suk, Yasemin Kaygusuz, Carson Kenum, et al. "Abstract A007: Emergence of metastasis-initiating cells during lung adenocarcinoma progression." Cancer Research 84, no. 22_Supplement (2024): A007. http://dx.doi.org/10.1158/1538-7445.tumbody-a007.
Full textAbstract:
Abstract Metastatic lung adenocarcinoma (LUAD) is responsible for the most cancer-related deaths worldwide, and only a subset of cells is capable of metastasizing. Our lab has previously shown that these metastasis-initiating cells express the transmembrane glycoprotein called L1CAM and exhibit characteristics of a fetal lung developmental continuum, ranging from early progenitor states to more differentiated states. The exact signal by which progenitor cells with high metastatic potentials are generated remains unknown. Here, we demonstrate that L1CAM facilitates the signaling cascades necessary to initiate and maintain metastasis-initiating cells in LUAD. Mechanistically, L1CAM interacts with the planar cell polarity (PCP) complex and activates the transcription factor c-Jun. Activated c-Jun, as part of the AP-1 complex, binds to enhancer sites of progenitor genes and promotes the emergence of a metastasis-capable progenitor state. Pharmacological ablation of these metastatic progenitor cells by a cytotoxic L1CAM antibody effectively eliminated LUAD metastasis in vivo. Our findings identify a novel L1CAM-mediated mechanism that maintains a progenitor state essential for metastasis and can be targeted therapeutically. Citation Format: Jin Suk Park, Yasemin Kaygusuz, Carson Kenum, Mohamed I. Gatie, Lan He, Roshan Sharma, Ronan Chaligné, Abdul G. Khan, Ivo C. Lorenz, Paul J. Balderes, Tuomas Tammela, Anna-Katerina Hadjantonakis, Karuna Ganesh, Charles M. Rudin, Joan Massagué. Emergence of metastasis-initiating cells during lung adenocarcinoma progression [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A007.
45
Yang, Beng, Xiaode Feng, Hua Liu, et al. "High-metastatic cancer cells derived exosomal miR92a-3p promotes epithelial-mesenchymal transition and metastasis of low-metastatic cancer cells by regulating PTEN/Akt pathway in hepatocellular carcinoma." Oncogene 39, no. 42 (2020): 6529–43. http://dx.doi.org/10.1038/s41388-020-01450-5.
Full textAbstract:
Abstract Exosomes play an important role in intercellular communication and metastatic progression of hepatocellular carcinoma (HCC). However, cellular communication between heterogeneous HCC cells with different metastatic potentials and the resultant cancer progression are not fully understood in HCC. Here, HCC cells with high-metastatic capacity (97hm and Huhm) were constructed by continually exerting selective pressure on primary HCC cells (MHCC-97H and Huh7). Through performing exosomal miRNA sequencing in HCC cells with different metastatic potentials (MHCC-97H and 97hm), many significantly different miRNA candidates were found. Among these miRNAs, miR-92a-3p was the most abundant miRNA in the exosomes of highly metastatic HCC cells. Exosomal miR92a-3p was also found enriched in the plasma of HCC patient-derived xenograft mice (PDX) model with high-metastatic potential. Exosomal miR-92a-3p promotes epithelial-mesenchymal transition (EMT) in recipient cancer cells via targeting PTEN and regulating its downstream Akt/Snail signaling. Furthermore, through mRNA sequencing in HCC cells with different metastatic potentials and predicting potential transcription factors of miR92a-3p, upregulated transcript factors E2F1 and c-Myc were found in high-metastatic HCC cells promote the expression of cellular and exosomal miR-92a-3p in HCC by directly binding the promoter of its host gene, miR17HG. Clinical data showed that a high plasma exosomal miR92a-3p level was correlated with shortened overall survival and disease-free survival, indicating poor prognosis in HCC patients. In conclusion, hepatoma-derived exosomal miR92a-3p plays a critical role in the EMT progression and promoting metastasis by inhibiting PTEN and activating Akt/Snail signaling. Exosomal miR92a-3p is a potential predictive biomarker for HCC metastasis, and this may provoke the development of novel therapeutic and preventing strategies against metastasis of HCC.
46
Pantina, Vincenzo Davide. "Abstract 5924: Intratumor heterogeneity in thyroid cancer progression." Cancer Research 83, no. 7_Supplement (2023): 5924. http://dx.doi.org/10.1158/1538-7445.am2023-5924.
Full textAbstract:
Abstract Thyroid cancer (CT) is the most common endocrine organs malignancy and is classified into:well-differentiated carcinomas, characterized by favourable prognosis and sensitive to standardtreatments, and undifferentiated carcinomas (UTC), the most lethal and highly refractoryagainst current therapies. UTCs have invasive and highly metastatic phenotype. The metastaticcascade model described distant metastasis origin deriving from cancer cells that seed to lymphnode and then disseminate to distant organs. According to this, lymphadenectomy was definedas an elective therapy for TC patients. However, recent TC trials discredit the improvement inpatient outcome. We aim to unveil the mechanism underlying tumor promotion, primary tumorclonal selection and TC metastatic origin determining which specific subclone is able to colonizedistant organs. Material and method:Thyroid carcinogenesis model was previously generated starting from human embryonic stemcells which underwent to a differentiation protocol. At day 22 of differentiation, thyroidprogenitor cells (TPCs) were engineered using CRISPR CAS-9 technology to introduce mutationin BRAFV600E/TP53R248Q and NRASQ61R/TP53R248Q gene in order to recapitulate, wheninjected in vivo, UTC. Double mutated TPCs were transduced with Barcode-mediated clonaltracking technology and subcutaneously/orthotopically injected in immunocompromisedmice. Results:We trasduced D22 double-mutated TPCs using highly complex lentiviral barcode library to mapclonal architecture in serial subcutaneous xenograft and multiple metastatic sites.Immunohistochemistry analysis obtained from P1 and P3 engraftment revealed conservation ofanaplastic thyroid cancer histologic features. Moreover, tumor-derived cells were in vitrocharacterized showing that P3 retains high migratory, invasion capacity and high MMP-9expression level, compared to P1. Transcriptomic analysis of P3 versus P1 derived cells showalso a critical metabolic switch. Cell derived from P3 engraftment were used to generateorthotopic model using Barcode mediated-clonal tracking technology. Conclusion:Given its impact on patient care, understanding the evolutionary history of anaplastic thyroidcarcinoma is critical in cancer treatment. Phylogenetic studies on the primary and metastatictumor should determine the emergence of one or more subclones, which have a crucial roleduring all the phases of tumor promotion, progression and metastatic onset. A phylogeneticanalysis performed via the barcode-mediated clonal tracking technology, will allow us to trackprimary tumor cellular clones selection and the arising progenity, determining their role in themetastatic cascade. NGS Analysis and RNA-Seq technology will define a specific primary tumor vs metastatic signature. The identification of cellular clones enriched in the metastasis willprovide new prognostic markers for metastatic thyroid carcinoma. Citation Format: Vincenzo Davide Pantina. Intratumor heterogeneity in thyroid cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5924.
47
Oh-Hohenhorst, Su Jung, and Tobias Lange. "Role of Metastasis-Related microRNAs in Prostate Cancer Progression and Treatment." Cancers 13, no. 17 (2021): 4492. http://dx.doi.org/10.3390/cancers13174492.
Full textAbstract:
Prostate cancer (PCa) is one of the most prevalent cancer types in males and the consequences of its distant metastatic deposits are the leading cause of PCa mortality. Therefore, identifying the causes and molecular mechanisms of hematogenous metastasis formation is of considerable clinical importance for the future development of improved therapeutic approaches. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNAs. Numerous studies have identified miRNAs as promotors or inhibitors of metastasis and revealed, in part, their targeting pathways in PCa. Because miRNAs are remarkably stable and can be detected in both tissue and body fluid, its potential as specific biomarkers for metastasis and therapeutic response is also currently under preclinical evaluation. In the present review, we focus on miRNAs that are supposed to initiate or suppress metastasis by targeting several key mRNAs in PCa. Metastasis-suppressing miRNAs include miR-33a-5p, miR-34, miR-132 and miR-212, miR-145, the miR-200 family (incl. miR-141-3p), miR-204-5p, miR-532-3p, miR-335, miR-543, miR-505-3p, miR 19a 3p, miR-802, miR-940, and miR-3622a. Metastasis-promoting RNAs, such as miR-9, miR-181a, miR-210-3, miR-454, miR-671-5p, have been shown to increase the metastatic potential of PCa cells. Other metastasis-related miRNAs with conflicting reports in the literature are also discussed (miR-21 and miR-186). Finally, we summarize the recent developments of miRNA-based therapeutic approaches, as well as current limitations in PCa. Taken together, the metastasis-controlling miRNAs provide the potential to be integrated in the strategy of diagnosis, prognosis, and treatment of metastatic PCa. Nevertheless, there is still a lack of consistency between certain miRNA signatures and reproducibility, which impedes clinical implementation.
48
Radojkovic, Milan, Jasmina Gligorijevic, Miroslav Stojanovic, Goran Stanojevic, and Ivan Ilic. "Laparotomy site implantation metastasis of carcinoma of the papilla of Vater." Scottish Medical Journal 62, no. 3 (2017): 119–21. http://dx.doi.org/10.1177/0036933017715958.
Full textAbstract:
Introduction Carcinomas of the papilla of Vater make up a heterogeneous group of tumours arising from different types of epithelium. Regional lymph nodes, liver and lungs are the primary sites of metastatic progression of these tumours. Case presentation We present a patient with an abdominal incision site metastasis of low-grade (mixed type) adenocarcinoma of the papilla of Vater one year after pylorus-preserving pancreaticoduodenectomy. Implantation metastasis of low-grade ampullary carcinoma in the laparotomy wound after open Whipple’s procedure is unusual. Conclusion Adjuvant chemoradiation might be considered for patients with low-grade localised disease as a potentially preventative measure vs. metastatic progression.
49
Zelefsky, Michael J., James A. Eastham, Angel M. Cronin, et al. "Metastasis After Radical Prostatectomy or External Beam Radiotherapy for Patients With Clinically Localized Prostate Cancer: A Comparison of Clinical Cohorts Adjusted for Case Mix." Journal of Clinical Oncology 28, no. 9 (2010): 1508–13. http://dx.doi.org/10.1200/jco.2009.22.2265.
Full textAbstract:
Purpose We assessed the effect of radical prostatectomy (RP) and external beam radiotherapy (EBRT) on distant metastases (DM) rates in patients with localized prostate cancer treated with RP or EBRT at a single specialized cancer center. Patients and Methods Patients with clinical stages T1c-T3b prostate cancer were treated with intensity-modulated EBRT (≥ 81 Gy) or RP. Both cohorts included patients treated with salvage radiotherapy or androgen-deprivation therapy for biochemical failure. Salvage therapy for patients with RP was delivered a median of 13 months after biochemical failure compared with 69 months for EBRT patients. DM was compared controlling for patient age, clinical stage, serum prostate-specific antigen level, biopsy Gleason score, and year of treatment. Results The 8-year probability of freedom from metastatic progression was 97% for RP patients and 93% for EBRT patients. After adjustment for case mix, surgery was associated with a reduced risk of metastasis (hazard ratio, 0.35; 95% CI, 0.19 to 0.65; P < .001). Results were similar for prostate cancer–specific mortality (hazard ratio, 0.32; 95% CI, 0.13 to 0.80; P = .015). Rates of metastatic progression were similar for favorable-risk disease (1.9% difference in 8-year metastasis-free survival), somewhat reduced for intermediate-risk disease (3.3%), and more substantially reduced in unfavorable-risk disease (7.8% in 8-year metastatic progression). Conclusion Metastatic progression is infrequent in men with low-risk prostate cancer treated with either RP or EBRT. RP patients with higher-risk disease treated had a lower risk of metastatic progression and prostate cancer–specific death than EBRT patients. These results may be confounded by differences in the use and timing of salvage therapy.
50
Izraely, Sivan, Shlomit Ben-Menachem, Sapir Malka, et al. "The Vicious Cycle of Melanoma-Microglia Crosstalk: Inter-Melanoma Variations in the Brain-Metastasis-Promoting IL-6/JAK/STAT3 Signaling Pathway." Cells 12, no. 11 (2023): 1513. http://dx.doi.org/10.3390/cells12111513.
Full textAbstract:
Previous studies from our lab demonstrated that the crosstalk between brain-metastasizing melanoma cells and microglia, the macrophage-like cells of the central nervous system, fuels progression to metastasis. In the present study, an in-depth investigation of melanoma-microglia interactions elucidated a pro-metastatic molecular mechanism that drives a vicious melanoma-brain-metastasis cycle. We employed RNA-Sequencing, HTG miRNA whole transcriptome assay, and reverse phase protein arrays (RPPA) to analyze the impact of melanoma-microglia interactions on sustainability and progression of four different human brain-metastasizing melanoma cell lines. Microglia cells exposed to melanoma-derived IL-6 exhibited upregulated levels of STAT3 phosphorylation and SOCS3 expression, which, in turn, promoted melanoma cell viability and metastatic potential. IL-6/STAT3 pathway inhibitors diminished the pro-metastatic functions of microglia and reduced melanoma progression. SOCS3 overexpression in microglia cells evoked microglial support in melanoma brain metastasis by increasing melanoma cell migration and proliferation. Different melanomas exhibited heterogeneity in their microglia-activating capacity as well as in their response to microglia-derived signals. In spite of this reality and based on the results of the present study, we concluded that the activation of the IL-6/STAT3/SOCS3 pathway in microglia is a major mechanism by which reciprocal melanoma-microglia signaling engineers the interacting microglia to reinforce the progression of melanoma brain metastasis. This mechanism may operate differently in different melanomas.