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Journal articles on the topic 'Drug re-profiling'

Author: Grafiati

Published: 5 June 2025

Last updated: 2 August 2025

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1

Mizushima, Tohru, and Takushi Namba. "Drug re-profiling strategy for drug development." Drug Delivery System 26, no. 2 (2011): 106–12. http://dx.doi.org/10.2745/dds.26.106.

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Ayyar, Porkodi, and Umamaheswari Subramanian. "Repurposing – second life for drugs." Pharmacia 69, no. (1) (2022): 51–59. https://doi.org/10.3897/pharmacia.69.e72548.

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Drug repurposing refers to finding new indications for existing drugs. The paradigm shift from traditional drug discovery to drug repurposing is driven by the fact that new drug pipelines are getting dried up because of mounting Research & Development (R&D) costs, long timeline for new drug development, low success rate for new molecular entities, regulatory hurdles coupled with revenue loss from patent expiry and competition from generics. Anaemic drug pipelines along with increasing demand for newer effective, cheaper, safer drugs and unmet medical needs call for new strategies of dr

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Mizushima, T. "Drug discovery and development focusing on existing medicines: drug re-profiling strategy." Journal of Biochemistry 149, no. 5 (2011): 499–505. http://dx.doi.org/10.1093/jb/mvr032.

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Dr, Gyansagar Kushwaha, K. Shrman Dr., Chetna Sharma Dr., and Gayatri Singh Dr. "Drug repurposing." Pharma innovation 9, no. 11 (2022): : 2101–207. https://doi.org/10.5281/zenodo.8282942.

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Drug repurposing is the process of finding new therapeutic applications for previously used, available or older medications. Drug repurposing, refers to a set of approaches that aim to adapt the current pharmacological effects to new applications. Repurposing can help uncover new medicines for diseases at a low cost and in less time. Availability of prior knowledge regarding safety, efficacy and the appropriate route of administration significantly reduces the development costs and cuts down the development time resulting in less effort required for successfully bringing a repositioned drug to

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Mahmoud, Zeinab, Mohamed M. Ismail, Mona Kamel, and Amira Youssef. "Levofloxacin reposition-based design: synthesis, biological evaluation of new levofloxacin derivatives targeting topoisomerase II beta polymerase as promising anticancer agents, molecular docking, and physicochemical characterization." RSC Advances 14, no. 38 (2024): 28098–119. http://dx.doi.org/10.1039/d4ra03975k.

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Akimov, Yevhen, and Tero Aittokallio. "Re-defining synthetic lethality by phenotypic profiling for precision oncology." Cell Chemical Biology 28, no. 3 (2021): 246–56. http://dx.doi.org/10.1016/j.chembiol.2021.01.026.

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Irham, Lalu Muhammad, Danang Prasetyaning Amukti, Wirawan Adikusuma, et al. "Trends in drug repurposing for chronic hepatitis-B infection: Bibliometric-based approach 1990-2024." BIO Web of Conferences 148 (2024): 04003. https://doi.org/10.1051/bioconf/202414804003.

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Chronic hepatitis B (CHB) infection is still a world problem today, especially in the developing countries. Until now, treatment related to CHB is still being continuously pursued using a variety of the latest approaches. One of today’s scientific efforts that can accelerate drug discovery for CHB is by using the concept of drug repurposing or drug repositioning. Our research drug trends using a drug repurposing approach for CHB from 1990-2024. To find the related data, we used some words include “drug repurposing, drug repositioning, drug retasking, drug re- profiling, drug recycling, drug re

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Entonu, Moses Edache, Mbateudi Danjuma IKA, Ekpa Emmanuel, Clifford Liki Barnabas, Daniel Danladi Gaiya, and Stella Kuyet UDU. "Drug repurposing: Recent advancements, challenges, and future therapeutics for cancer treatment." Journal of Bacteriology & Mycology: Open Access 10, no. 2 (2022): 26–30. http://dx.doi.org/10.15406/jbmoa.2022.10.00322.

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Cancer is a prime public health burden that accounts for approximately 9.9 million deaths worldwide. Despite recent advances in treatment regimen and huge capital investment in the pharmaceutical sector, there has been little success in improving the chances of survival of cancer patients. Drug repurposing sometimes termed drug repositioning is a strategy of discovery and redeveloping existing drugs for new therapeutic purposes. This novel approach is highly efficient, considerably cuts research and development costs, reduces the drug development timeline, maximizes therapeutic value and conse

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Williams, Kevin P., Jennifer L. Allensworth, Shalonda M. Ingram, et al. "Quantitative high-throughput efficacy profiling of approved oncology drugs in inflammatory breast cancer models of acquired drug resistance and re-sensitization." Cancer Letters 337, no. 1 (2013): 77–89. http://dx.doi.org/10.1016/j.canlet.2013.05.017.

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Brüggenthies, Johanna B., Jakob Dittmer, Eva Martin, et al. "Insights into the Identification of iPSC- and Monocyte-Derived Macrophage-Polarizing Compounds by AI-Fueled Cell Painting Analysis Tools." International Journal of Molecular Sciences 25, no. 22 (2024): 12330. http://dx.doi.org/10.3390/ijms252212330.

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Macrophage polarization critically contributes to a multitude of human pathologies. Hence, modulating macrophage polarization is a promising approach with enormous therapeutic potential. Macrophages are characterized by a remarkable functional and phenotypic plasticity, with pro-inflammatory (M1) and anti-inflammatory (M2) states at the extremes of a multidimensional polarization spectrum. Cell morphology is a major indicator for macrophage activation, describing M1(-like) (rounded) and M2(-like) (elongated) states by different cell shapes. Here, we introduced cell painting of macrophages to b

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Wang, Qiang, Zhijuan Lin, and Qing Yi. "RAR Gamma Activation Sensitizes Human Myeloma Cells to Carfilzomib Treatment through OAS-RNase L Innate Immune Pathway." Blood 136, Supplement 1 (2020): 36–37. http://dx.doi.org/10.1182/blood-2020-133970.

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Proteasome inhibitors (PIs) such as bortezomib (Btz) and carfilzomib (Cfz) kill MM cells by disrupting the degradation of misfolded proteins, presumably derived from high-level immunoglobulin production, which provides an appealing explanation for why MM cells are so uniquely sensitive to PIs. However, relapses are frequent and acquired resistance to PI treatment emerges in most patients. Therefore, identifying novel and safe drugs overcoming PI resistance in MM will aid in chemo-(re)sensitization, reducing PI-induced side effects, and maximizing the outcomes of PI therapy. Here we performed a

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Dufva, Olli, Matti Kankainen, Tiina Kelkka, et al. "Mutational Landscape of Aggressive Natural Killer Cell Leukemia and Drug Sensitivity Profiling Reveal Therapeutic Options in Natural Killer Cell Malignancies." Blood 128, no. 22 (2016): 2921. http://dx.doi.org/10.1182/blood.v128.22.2921.2921.

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Abstract INTRODUCTION Natural killer (NK) cell malignancies are rare aggressive neoplasms that are classified by the WHO as extranodal NK/T-cell lymphoma, nasal type (NKTCL) and aggressive NK-cell leukemia (ANKL). Recently, genome and exome level studies in NKTCL have shed light on the mutational spectrum of the disease. However, somatic mutations in ANKL have not been characterized. Here, we identified somatic mutations in 14 cases of ANKL to further clarify the genetic landscape underlying malignant NK cell proliferation. We compared the discovered variants to those detected in NKTCL to unde

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Islam, Shariful, Andrew Paek, Michael Hammer, et al. "Multi-Omics of Aurora Inhibition Induced Polyploidy Reveals Mechanisms of Disease Relapse in MYC/BCL2-Addicted High Grade B-Cell Lymphoma." Blood 132, Supplement 1 (2018): 1572. http://dx.doi.org/10.1182/blood-2018-99-109975.

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Abstract Key Points MYC mediated upregulation of TPX2, KPNA2 and RanGAP1 dysregulate the spindle assembly checkpoint in drug-induced polyploid cells. Drug-induced polyploid cells re-enter cell cycle via multipolar mitosis, fission or budding, a mechanism of disease relapse. Abstract Double-hit (DH) or double-expresser (DE) diffuse large B-cell lymphomas (DLBCL) are high-grade B-cell lymphomas that are mostly incurable with standard chemo-immunotherapy due to treatment resistance. The generation of drug-induced aneuploid/polyploid (DIAP) cells is a common effect of anti-DLBCL therapies (e.g. vi

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Fedorenko, А. S., А. Т. Burbello, М. А. Korosteleva, М. V. Pokladova, and E. L. Lataria. "Financial burden of COVID-19 for a hospital-type medical organization." Pharmacoeconomics: theory and practice 10, no. 3 (2022): 26–33. http://dx.doi.org/10.30809/phe.3.2022.5.

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OBJECTIVES. To assess the structure of spending the financial resources of hospital for the purchase of medicines for the treatment of patients with COVID-19 on North-Western State Medical University. I.I. Mechnikov for the period of reprofiling during 2020-2021. Also to conduct a comparative analysis with the costs of treating patients who received treatment in non-reprofiled units. Materials and methods. With the help of ABC/VEN and ATC/DDD analyzes, the consumption of drugs used to treat patients with COVID-19, as well as for non-repurposed units, was estimated. Results. An analysis was mad

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Limaye, Akanksha, Jajoriya Sweta, Maddala Madhavi, et al. "In Silico Insights on GD2 : A Potential Target for Pediatric Neuroblastoma." Current Topics in Medicinal Chemistry 19, no. 30 (2020): 2766–81. http://dx.doi.org/10.2174/1568026619666191112115333.

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Background: Originating from the abnormal growth of neuroblasts, pediatric neuroblastoma affects the age group below 15 years. It is an aggressive heterogenous cancer with a high morbidity rate. Biological marker GD2 synthesised by the GD2 gene acts as a powerful predictor of neuroblastoma cells. GD2 gangliosides are sialic acid-containing glycosphingolipids. Differential expression during brain development governs the function of the GD2. The present study explains the interaction of the GD2 with its established inhibitors and discovers the compound having a high binding affinity against the

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Van Ness, Brian, Holly A. F. Stessman, Linda B. Baughn, et al. "Strategies To Identify Effective Treatments For Proteasome Inhibitor Resistant Multiple Myeloma." Blood 122, no. 21 (2013): 278. http://dx.doi.org/10.1182/blood.v122.21.278.278.

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Abstract Despite the introduction of effective new agents in the treatment of myeloma, the disease is still mostly incurable. Among the most significant issues is the heterogeneity of the disease, with accumulation of multiple genetic abnormalities among patients, resulting in disease refractory to some highly active agents, or the emergence of resistance leading to aggressive relapse. We have focused efforts on modeling drug sensitivity, and generating both genetic and biomarker signatures of response and resistance to the proteasome inhibitors (PIs): bortezomib (Btz), MLN2238 (Takeda) and ca

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Sureda, Manuel, Joseba Rebollo, Ramón González-Manzano, et al. "Transcriptome (RNA next generation sequencing) for personalizing of cancer treatment: A correlation with previous clinical resistance." Journal of Clinical Oncology 39, no. 15_suppl (2021): e15046-e15046. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.e15046.

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e15046 Background: RNA Next Generation Sequencing (transcriptome) is a potential useful tool to predict chemoresistance to available anticancer drug therapy. A correlation between previous clinical resistance and drug resistance profiling according to RNA NGS results has been studied. Methods: Since March 2018, whole transcriptome RNA NGS has been performed using Ion-Torrent GeneStudio S5 System in fresh-frozen biopsies obtained from tru-cut or surgical excision procedures from patients with resistant metastatic cancer. We have selected patients with clinically unequivocal drug resistance to p

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Domanskyi, Sergii, Todd B. Sheridan, Brian J. Sanderson, et al. "Abstract A010: Longitudinal histology and spatial transcriptomics profiling in targeted treatment of melanoma patient-derived models interrogates persister and resistant cell populations." Cancer Research 84, no. 3_Supplement_2 (2024): A010. http://dx.doi.org/10.1158/1538-7445.canevol23-a010.

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Abstract Over half of BRAF-mutant melanoma patients with initial response to targeted therapy will recur with resistant disease. It is thought that recurrence arises from the ability of resistant clonal populations to enter and exit a slow-cycling persister state, evading treatment in quiescence before returning to a proliferative state. However, clonal transcriptional profiles and their spatial relationships in the tumor environment are not well characterized. Through longitudinal profiling of tumors from pre-treatment through the growth of resistant tumors, we track clonal lineages and trans

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Patidar, Mohini, Raghvendra Dubey, Sunita Minz, Madhulika Pradhan, and Nitin Deshmukh. "A mechanism-driven strategy for in-silico prediction, molecular docking, synthesis, and biological assessment of substituted 1,3,4-oxadiazole derivatives as novel antidiabetic agents." Journal of Applied Pharmaceutical Research 13, no. 2 (2025): 194–203. https://doi.org/10.69857/joapr.v13i2.1031.

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Background: Diabetes mellitus is a long-standing and debilitating metabolic condition that imposes a substantial global health burden, leading to severe and widespread complications. Objectives: This study aims to predict physicochemical properties of 1,3,4-oxadiazole derivatives using in-silico methods and molecular docking simulations to explore their potential as α-glucosidase inhibitors for diabetes management. Furthermore, this study aims to experimentally synthesize and characterize these derivatives to validate their inhibitory activity. Methods: In silico drug-likeness, pharmacokinetic

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Renatino-Canevarolo, Rafael, Praneeth Reddy Sudalagunta, Maria D. Coelho Siqueira Silva, et al. "Re-Constructing and Exploiting Transcriptional Regulatory Networks in Multiple Myeloma Drug Resistance." Blood 134, Supplement_1 (2019): 5544. http://dx.doi.org/10.1182/blood-2019-128442.

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Problem: Multiple myeloma (MM) is a treatable yet incurable hematologic cancer that lacks predictive biomarkers. Approach: Here we apply a systems biology approach to determine patient-specific mechanisms, as well as signatures of drug resistance in MM. To achieve this goal, we have combined ex vivo drug sensitivity data from 307 MM fresh primary samples tested with 162 drugs and combinations, with paired molecular data (RNAseq and mutational profiling) from a larger overlapping cohort of 606 MM samples from Moffitt's Multiple Myeloma Working Group (MMWG) repository in collaboration with M2Gen

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Aleshin, Alexey, Marianne A. Santaguida, Michael A. Spinner, et al. "Ex Vivo Drug Response Profiling Defines Novel Drug Sensitivity Patterns for Predicting Clinical Therapeutic Responses in Myeloid Neoplasms." Blood 132, Supplement 1 (2018): 4356. http://dx.doi.org/10.1182/blood-2018-99-120146.

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Abstract Introduction: Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML) are clonal myeloid neoplasms for which limited conventional treatment options exist in the relapsed / refractory setting, especially for older patients. Methods: We provide proof of concept data by drug sensitivity profiling of 64 samples from 52 adult patients with both newly diagnosed and treatment refractory myeloid neoplasms (MDS = 38, CMML = 4, AML = 10). Fresh mononuclear cells from bone marrow aspirates and/or peripheral blood specimens were red blood cell lyse

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Chanan-Khan, Asher Alban, Noreen Ersing, Paula Pera, et al. "Characterization of Bortezomib Resistant Human Multiple Myeloma Cell Line (HMCL): A Clinically Relevant Model for Novel Drug Development in Multiple Myeloma (MM)." Blood 108, no. 11 (2006): 5050. http://dx.doi.org/10.1182/blood.v108.11.5050.5050.

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Abstract Introduction: Bortezomib (B) is the first in class proteasome inhibitor that received FDA approval for the treatment of MM patients with relapsed or refractory disease. Despite impressive clinical activity all patients develop resistance to B. The underlying mechanism of resistance to B remains undetermined. Mechanisms to overcome B resistance or development of new therapeutic agent(s) with activity in context of B resistance are limited due to unavailability of established preclinical B resistant MM models. To overcome this challenge we developed a B resistant HMCL. Methods: we chron

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Sboev, Alexander, Anton Selivanov, Ivan Moloshnikov, et al. "Extraction of the Relations among Significant Pharmacological Entities in Russian-Language Reviews of Internet Users on Medications." Big Data and Cognitive Computing 6, no. 1 (2022): 10. http://dx.doi.org/10.3390/bdcc6010010.

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Nowadays, the analysis of digital media aimed at prediction of the society’s reaction to particular events and processes is a task of a great significance. Internet sources contain a large amount of meaningful information for a set of domains, such as marketing, author profiling, social situation analysis, healthcare, etc. In the case of healthcare, this information is useful for the pharmacovigilance purposes, including re-profiling of medications. The analysis of the mentioned sources requires the development of automatic natural language processing methods. These methods, in turn, require t

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Milchevskaya, Vladislava, Grischa Tödt, and Toby James Gibson. "A Tool to Build Up-To-Date Gene Annotations for Affymetrix Microarrays." Genomics and Computational Biology 3, no. 2 (2017): 38. http://dx.doi.org/10.18547/gcb.2017.vol3.iss2.e38.

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Genome-wide expression profiling and genotyping is widely applied in functional genomics research, ranging from stem cell studies to cancer, in drug response studies, and in clinical diagnostics. The Affymetrix GeneChip microarrays represent the most popular platform for such assays. Nevertheless, due to rapid and continuous improvement of the knowledge about the genome, the definition of many of the genes and transcripts change, and new genes are discovered. Thus the original probe information is out-dated for a number of Affymetrix platforms, and needs to be re-defined. It has been demonstra

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Illangeswaran, Raveen Stephen, Daniel Zechariah Jebanesan, Kezia Kanimozhi Sivakumar, et al. "Abstract 3973: Transcriptomic profiling of in-vitro modelled drug resistant AML cell lines unravel metabolic and stemness gene signatures." Cancer Research 82, no. 12_Supplement (2022): 3973. http://dx.doi.org/10.1158/1538-7445.am2022-3973.

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Abstract Disease recurrence is the major cause of treatment failure and mortality in acute myeloid leukemia (AML). A small fraction of leukemic cells that withstand chemotherapeutic insult can rewire cellular processes to re-emerge with lethal disease. Approaches to decipher drug resistance mechanisms in these drug persister cells can pave the way for newer therapies and improve survival in patients. To uncover drug resistant mechanisms that are clinically relevant, we generated in-house Cytarabine (AraC) and Arsenic trioxide (ATO) resistant cells from naïve MV4-11 AML cell line by incremental

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Ochsner, Anna M., Kelsey E. Huntington, Lanlan Zhou, Benedito Carneiro, and Wafik El-Deiry. "Abstract 2593: Combined ATR+PARP inhibition exhibits potent synergy in colorectal and pancreatic cancer cytotoxicity." Cancer Research 82, no. 12_Supplement (2022): 2593. http://dx.doi.org/10.1158/1538-7445.am2022-2593.

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Abstract Precision medicine continues to expand treatment options for patients tailored to tumor phenotype. In homologous recombination (HR) deficient cancers like those with BRCA1/2-mutations, inhibition of poly (ADP-ribose) polymerase (PARP) has shown improved mortality compared to older gold standard therapies like DNA damaging agents. Unfortunately estimates upward of 40% of patients develop resistance to PARP inhibitor monotherapy during the course of their treatment. We explored potential synergistic drug combinations to re-sensitize tumors with acquired PARP inhibitor resistance in panc

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Bjorklund, Chad C., Deborah J. Kuhn, Jairo A. Matthews, Michael Wang, Veerabhadran Baladandayuthapani та Robert Z. Orlowski. "Activation of the Wnt/β-Catenin Pathway Mediates Lenalidomide Resistance in Multiple Myeloma." Blood 114, № 22 (2009): 113. http://dx.doi.org/10.1182/blood.v114.22.113.113.

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Abstract Abstract 113 Background: Novel drugs such as the immunomodulatory agent lenalidomide have revolutionized the treatment of multiple myeloma, as evidenced by an increasing overall survival for patients with both newly-diagnosed, and relapsed and/or refractory disease. Despite these improvements, myeloma remains incurable, and is still characterized by a trend for increasing chemoresistance at relapse, with a decreasing duration of benefit from each successive line of therapy. By understanding the mechanisms responsible for the emergence of drug resistance, which have so far not been wel

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Häupl, Thomas, Mehdi Yahyawi, Carsten Lübke, et al. "Gene Expression Profiling of Rheumatoid Arthritis Synovial Cells Treated with Antirheumatic Drugs." Journal of Biomolecular Screening 12, no. 3 (2007): 328–40. http://dx.doi.org/10.1177/1087057107299261.

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Nonbiological therapeutics are frequently used for the treatment of patients with rheumatoid arthritis (RA). Because the mechanisms of action of these therapeutics are unclear, the authors aimed to elucidate the molecular effects of typical antirheumatic drugs on the expression profile of RA-related genes expressed in activated synovial fibroblasts. For reasons of standardization and comparability, immortalized synovial fibroblasts derived from RA (RASF) and normal donors (NDSF) were treated with methotrexate, prednisolone, or diclofenac and used for gene expression profiling with oligonucleot

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Agampodi Dewa, Amila, Zeinab G. Khalil, Ahmed H. Elbanna, and Robert J. Capon. "Chrysosporazines Revisited: Regioisomeric Phenylpropanoid Piperazine P-Glycoprotein Inhibitors from Australian Marine Fish-Derived Fungi." Molecules 27, no. 10 (2022): 3172. http://dx.doi.org/10.3390/molecules27103172.

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A library of fungi previously recovered from the gastrointestinal tract (GIT) of several fresh, commercially sourced Australian mullet fish was re-profiled for production of a rare class of phenylpropanoid piperazine alkaloids (chrysosporazines) using an integrated platform of; (i) miniaturized 24-well plate cultivation profiling (MATRIX), (ii) UPLC-DAD and UPLC-QTOF-MS/MS (GNPS) chemical profiling, and; (iii) precursor directed biosynthesis to manipulate in situ biosynthetic performance and outputs; to detect two new fungal producers of chrysosporazines. Chemical analysis of an optimized PDA

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Leung, Carmen Oi, Yang Yang, Karl Kam So, Qian Zhao, and Terence Kin Lee. "Abstract 1746: Broad-spectrum kinome profiling identifies CDK6 upregulation as a driver of lenvatinib resistance in hepatocellular carcinoma." Cancer Research 83, no. 7_Supplement (2023): 1746. http://dx.doi.org/10.1158/1538-7445.am2023-1746.

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Abstract Lenvatinib is the FDA-approved targeted drug for advanced hepatocellular carcinoma (HCC), but the efficacy is modest due to drug resistance. Tumor kinome re-wiring governs drug resistance in resistant cancer cells, which is an obstacle for efficient cancer therapy. Therefore, identification of the kinases critical for this rewiring process in HCC is crucial. Upon mass spectrometry analysis using a lysine-targeted sulfonyl fluoride probe named XO44, CDK6 was identified to be the most upregulated kinase in lenvatinib-resistant HCC cell lines. Lentiviral-based overexpression and knockdow

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Nadzri, Ainol Hayah Ahmad, Dzulkiflee Ismail, Saravana Kumar Jayaram, Noor Zuhartini Md Muslim, and Wan Nur Syuhaila Mat Desa. "Precursor Profiling of Extracted Pseudoephedrine Using Gas Chromatography-Mass Spectrometry (GCMS) in Conjunction with Chemometric Procedure." Materials Science Forum 1025 (March 2021): 209–18. http://dx.doi.org/10.4028/www.scientific.net/msf.1025.209.

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Various methods for the clandestine manufacture of amphetamine-type stimulant (ATS) involve the extraction and subsequent reaction of pseudoephedrine salts with other essential chemicals. The precursor seized in clandestine laboratory operation is supplied from illegal sources or clandestinely extracted from decongestant tablets (despite the presence of excipients that serve to hamper re-extraction). This work reports the organic profiling of pseudoephedrine from a simulated clandestine extract of different decongestant tablets formulations. The study aims to determine the feasibility of the c

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Nagy, Ivett. "Drug crime transformation under the effect of online platforms." Belügyi Szemle 69, no. 6. ksz. (2021): 107–23. http://dx.doi.org/10.38146/bsz.spec.2021.6.7.

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Many types of drug crimes are already known, but it is common to offender groups to implement them in an organised, coordinated, multi-level framework. Affected by online platforms, drug crimes are undergoing a transformation that presents new challenges for the authorities. Criminal groups also like to (re)take the opportunities offered by the Internet. Platforms that connect to the Dark Web, the Dark Internet (secret network form), have become increasingly popular over the past few years, thanks to the fact that there are also services available which are not available by traditional browser

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Rocchi, Laura, Andrea Faenza, Laura Rambelli, et al. "Ex-Vivo Drug Response Profiling for Precision Medicine Approaches in Acute Myeloid Leukemia with the Open Microwell Microfluidic Platform." Blood 128, no. 22 (2016): 1675. http://dx.doi.org/10.1182/blood.v128.22.1675.1675.

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Abstract Background: Patient stratification to match individual patients with the most effective drug treatment is still a major open challenge in cancer care. For instance, cytarabine is the main drug used for AML treatment but 30% of patients fail to respond to this agent. Laboratory developed tests determining ex-vivo cellular response to cytotoxic anticancer drugs have demonstrated good correlations with clinical response, sometimes surpassing the predictive power of molecular and genetic profiling. Standardizing sample processing to remove operator-dependent biases and maintaining live ce

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Hunter, Z., J. Sun, H. Tseng, et al. "TNF-a, retinoid acid and STAT4 pathways are differentially regulated by the HDAC inhibitors, SAHA, TSA and Sirtinol in Waldenstrom's Macroglobulinemia." Journal of Clinical Oncology 27, no. 15_suppl (2009): e14582-e14582. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e14582.

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e14582 Background: HDAC inhibitors (HDAC-I) have emerged as a promising class of therapeutics for the treatment of lymphoplasmacytic malignancies, particularly in combination strategies. The basic mechanisms by which these agents modulate malignant cell growth remain to be clarified. In recent studies, we showed that SAHA, TSA, and Sirtinol have significant preclinical activity in Waldenstrom's macroglobulinemia (WM). As part of our effort to identify potential molecular targets for these agents, we performed gene expression profiling (GEP) using WM cells treated with these agents. Methods: We

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Lipinski, Lindsay, Ajay Abad, Laszlo Mechtler, et al. "INNV-16. CLINICAL APPLICABILITY OF INDIVIDUALIZED DRUG RESPONSE PROFILING UTILIZING EX-VIVO TISSUE-DERIVED 3D CELL CULTURE ASSAYS IN HIGH-GRADE GLIOMA: A SINGLE INSTITUTION CASE SERIES USING 3D-PREDICT RESULTS." Neuro-Oncology 22, Supplement_2 (2020): ii119—ii120. http://dx.doi.org/10.1093/neuonc/noaa215.499.

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Abstract Recurrent high-grade glioma is a challenging disease process, without consensus on effective second-line therapy options. Individualized, patient-specific, biologically-based data is desirable in driving therapeutic decision-making. Patients with recurrent high-grade glioma and planned surgical re-resection at our institution were prospectively enrolled into the 3D-PREDICT study. Tissue was collected at the time of surgery for ex vivo 3D cell culture assays comprising a panel of agents commonly used for high-grade glioma, including chemotherapies and targeted therapies used in other s

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Lin, Joanne, Stacey L. Lee, Anna M. Russell, et al. "A structure-based engineering approach to abrogate pre-existing antibody binding to biotherapeutics." PLOS ONE 16, no. 7 (2021): e0254944. http://dx.doi.org/10.1371/journal.pone.0254944.

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Development of biotherapeutics is hampered by the inherent risk of immunogenicity, which requires extensive clinical assessment and possible re-engineering efforts for mitigation. The focus in the pre-clinical phase is to determine the likelihood of developing treatment-emergent anti-drug antibodies (TE-ADA) and presence of pre-existing ADA in drug-naïve individuals as risk-profiling strategies. Pre-existing ADAs are routinely identified during clinical immunogenicity assessment, but their origin and impact on drug safety and efficacy have not been fully elucidated. One specific class of pre-e

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Yu, Chu-qin, Jian-ping Chen, Yan-mei Zhong, et al. "Metabolomic profiling of rat urine after oral administration of the prescription antipyretic Hao Jia Xu Re Qing Granules by UPLC/Q-TOF-MS." Biomedical Chromatography 32, no. 11 (2018): e4332. http://dx.doi.org/10.1002/bmc.4332.

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Angelopoulos, Panagiotis Agisilaos, Antonio Passaro, Ilaria Attili, et al. "Management of MET-Driven Resistance to Osimertinib in EGFR-Mutant Non-Small Cell Lung Cancer." Genes 16, no. 7 (2025): 772. https://doi.org/10.3390/genes16070772.

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Epidermal growth factor receptor (EGFR) mutations occur in approximately 10–20% of Caucasian and up to 50% of Asian patients with oncogene-addicted non-small cell lung cancer (NSCLC). Most frequently, alterations include exon 19 deletions and exon 21 L858R mutations, which confer sensitivity to EGFR tyrosine kinase inhibitors (TKIs). In the last decade, the third-generation EGFR-TKI osimertinib has represented the first-line standard of care for EGFR-mutant NSCLC. However, the development of acquired mechanisms of resistance significantly impacts long-term outcomes and represents a major thera

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Murugan, Poongkavithai Vadevoo Sri, Gunassekaran Gowri Rangaswamy, and Byungheon Lee. "Abstract 2870: Inhibition of DNA methylation and histone deacetylation synergistically reprograms M2-polarized macrophages and inhibits tumor growth by upregulating miR-7083-5p." Cancer Research 83, no. 7_Supplement (2023): 2870. http://dx.doi.org/10.1158/1538-7445.am2023-2870.

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Abstract Reactivation of epigenetically suppressed miRs, in tumors, have become increasingly relevant in clinical practice. But less epigenetic studies have been performed on tumor associated M2 macrophages that plays a key role in the functional regulation of epithelial cancer development. In this study, we used 5-Aza-2’5’Aza-deoxycytidine (Aza) or decitabine (5-Aza) plus Trichostatin A (TSA) as epigenetic drugs to study the M2 macrophage modulation in the tumor microenvironment. Epigenetic therapy, not only modulated the M2 macrophages to a tumoricidal phenotype, but also strengthened the tu

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Gambacorta, Valentina, Daniela Gnani, Laura Zito, et al. "Integrated Epigenetic Profiling Identifies EZH2 As a Therapeutic Target to Re-Establish Immune Recognition of Leukemia Relapses with Loss of HLA Class II Expression." Blood 134, Supplement_1 (2019): 514. http://dx.doi.org/10.1182/blood-2019-127395.

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Background It is becoming increasingly recognized that evasion from immune control represents one of the main drivers of acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (allo-HCT). In particular, alterations in the antigen processing and presentation machinery represent one of the most effective strategies enacted by tumor cells to avoid recognition from T cells. Whereas it is now well recognized that genomic loss of HLA is frequently at the basis of post-transplantation relapse, it was only recently reported that up to 40% of AML relapses display trans

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Ennis, Sarah, Alessandra Conforte, Sukhraj Pal Singh Dhami, Philippe Krebs, Michael O'Dwyer, and Eva Szegezdi. "Single Cell Transcriptomics Revealed Molecular Alterations in AML Cell Clusters Relevant to Refractory Disease at Relapse." Blood 138, Supplement 1 (2021): 3316. http://dx.doi.org/10.1182/blood-2021-153910.

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Abstract Introduction: Drug resistance at relapse is a major cause of mortality in AML. Previous genomic profiling of AML patient samples revealed that in many cases the mutational profile did not change between diagnosis and relapse (Parkin et al., Blood, 2013, Nuno K et al., Blood, 2020), indicating that epigenetic changes can have a substantial contribution to acquired drug resistance and refractory disease at relapse. In order to uncover such functional alterations, longitudinal AML patient samples collected at diagnosis, during remission and relapse were analysed with single cell transcri

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Chong, Stephen Jun Fei, Mary C. Collins, Liam Hackett, and Matthew S. Davids. "Re-Wiring BCL-2 Family Anti-Apoptotic Protein Dependencies through Modulating Phosphorylation to Re-Sensitize Venetoclax-Resistant Lymphoid Malignancies to BCL-2 Inhibition." Blood 136, Supplement 1 (2020): 35–36. http://dx.doi.org/10.1182/blood-2020-140455.

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Introduction Resistance to apoptosis is a hallmark of cancer, and modulation of BCL-2 family proteins is an important mediator of such resistance in hematologic malignancies. Despite the clinical efficacy of the BCL-2 inhibitor venetoclax (VEN), prolonged treatment may lead to resistance, such as the BCL2 G101V mutation (Blombery et al, Blood, 2020); however, over half of VEN resistant cases are not explained by known genetic mechanisms. Phosphorylation of BCL-2 at serine-70 (S70pBCL2) or of MCL-1 at threonine-163 (T163pMCL1) have been shown to increase sequestration of the pro-apoptotic prote

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Wang, Qiang, Dongyu Zhao, Miao Xian, et al. "MIF as a biomarker and therapeutic target for overcoming resistance to proteasome inhibitors in human myeloma." Blood 136, no. 22 (2020): 2557–73. http://dx.doi.org/10.1182/blood.2020005795.

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Abstract Multiple myeloma (MM) remains largely incurable despite significant advances in biotherapy and chemotherapy. The development of drug resistance is a major problem in MM management. Macrophage migration inhibitory factor (MIF) expression was significantly higher in purified MM cells from relapsed patients than those with sustained response, and MM patients with high MIF had significantly shorter progression-free survival (PFS) and overall survival (OS). MM cell lines also express high levels of MIF, and knocking out MIF made them more sensitive to proteasome inhibitor (PI)-induced apop

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Reale, Antonia, Tiffany Khong, Rong Xu, et al. "Abstract 3491: New targets and new approaches for multiple myeloma: Extracellular vesicles as functional liquid biomarkers." Cancer Research 82, no. 12_Supplement (2022): 3491. http://dx.doi.org/10.1158/1538-7445.am2022-3491.

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Abstract Background: We have previously demonstrated that stromal cells (HS5) pre-treated with small extracellular vesicles (sEV) enriched from blood plasma of myeloma (MM) patients promoted adhesion of human MM cell lines (HMCL), with preliminary proteomic profiling of MM-sEV (vs healthy donors-HD) revealing enrichment of factors implicated in cell migration and adhesion. Aims: To demonstrate that plasma-derived MM-sEV induce a microenvironment favoring MM progression and identify the protein content of plasma-sEV that promotes this. Methods: sEV were enriched from plasma (1mL) using a commer

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Reale, Antonia, Rong Xu, Irena Carmichael, et al. "Abstract 2366: Myeloma-derived circulating extracellular vesicles affect human stromal cell behaviour and promote tumor progression: A multi-omic approach." Cancer Research 83, no. 7_Supplement (2023): 2366. http://dx.doi.org/10.1158/1538-7445.am2023-2366.

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Abstract Background: We have shown that human stromal cells (HS5) treated with small extracellular vesicles (EV) derived from plasma of myeloma (MM) patients (MM-EV) promoted adhesion of human MM cell lines (HMCL), with preliminary proteomic profiling of MM- vs healthy donors HD-EV revealing enrichment of factors implicated in cell migration and adhesion. Aims: 1) Demonstrate that MM-EV induce the formation of a tumour microenvironment (TME) favouring MM progression; 2) identify the protein content of MM-EV promoting this; 3) discover signaling drivers of EV-mediated functional remodelling of

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Pilus, Nur Shazwani Mohd, Azira Muhamad, Muhammad Ashraf Shahidan, and Nurul Yuziana Mohd Yusof. "Potential of Epidermal Growth Factor-like Peptide from the Sea Cucumber Stichopus horrens to Increase the Growth of Human Cells: In Silico Molecular Docking Approach." Marine Drugs 20, no. 10 (2022): 596. http://dx.doi.org/10.3390/md20100596.

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The sea cucumber is prominent as a traditional remedy among Asians for wound healing due to its high capacity for regeneration after expulsion of its internal organs. A short peptide consisting of 45 amino acids from transcriptome data of Stichopus horrens (Sh-EGFl-1) shows a convincing capability to promote the growth of human melanoma cells. Molecular docking of Sh-EGFl-1 peptide with human epidermal growth factor receptor (hEGFR) exhibited a favorable intermolecular interaction, where most of the Sh-EGFl-1 residues interacted with calcium binding-like domains. A superimposed image of the do

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Mutungi, Moses Mutuse, Felix Wambua Muema, Festus Kimutai, et al. "Antioxidant and Antiproliferative Potentials of Ficus glumosa and Its Bioactive Polyphenol Metabolites." Pharmaceuticals 14, no. 3 (2021): 266. http://dx.doi.org/10.3390/ph14030266.

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Ficus glumosa Delile (Moraceae), a reputed plant that is used in herbal medicine, is of high medicinal and nutritional value in local communities primarily ascribed to its phytochemical profile. Currently, there are hardly any fine details on the chemical profiling and pharmacological evaluation of this species. In this study, the flavonoids and phenolics contents of the ethanol extracts and four extracted fractions (petroleum ether (PE), ethyl acetate (EA), n-butanol, and water) of the stem bark of Ficus glumosa were firstly quantified. Further, their antioxidant and antiproliferative potenti

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Singh, Komudi, Michelle Baird, Robert Fischer, et al. "Misregulation of ELK1, AP1, and E12 Transcription Factor Networks Is Associated with Melanoma Progression." Cancers 12, no. 2 (2020): 458. http://dx.doi.org/10.3390/cancers12020458.

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Melanoma is among the most malignant cutaneous cancers and when metastasized results in dramatically high mortality. Despite advances in high-throughput gene expression profiling in cancer transcriptomic studies, our understanding of mechanisms driving melanoma progression is still limited. We present here an in-depth bioinformatic analysis of the melanoma RNAseq, chromatin immunoprecipitation (ChIP)seq, and single-cell (sc)RNA seq data to understand cancer progression. Specifically, we have performed a consensus network analysis of RNA-seq data from clinically re-grouped melanoma samples to i

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Kam, Christina W., Jason G. Dumelie, Gabriele Ciceri, et al. "Sustained Epigenetic Reactivation in Fragile X Neurons with an RNA-Binding Small Molecule." Genes 16, no. 3 (2025): 278. https://doi.org/10.3390/genes16030278.

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Background/Objectives: Fragile X syndrome (FXS) is a disease of pathologic epigenetic silencing induced by RNA. In FXS, an expanded CGG repeat tract in the FMR1 gene induces epigenetic silencing during embryogenesis. FMR1 silencing can be reversed with 5-aza-deoxyctidine (5-aza-dC), a nonspecific epigenetic reactivator; however, continuous administration of 5-aza-dC is problematic due to its toxicity. We describe an approach to restore FMR1 expression in FXS neurons by transient treatment with 5-aza-dC, followed by treatment with 2HE-5NMe, which binds the CGG repeat expansion in the FMR1 mRNA

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Lee, You Won, Eun Ji Lee, Seung Yeon Oh, et al. "Abstract 5935: Phenotype profiling of tumor microenvironment in EGFR mutant lung adenocarcinoma with multi-omics data." Cancer Research 83, no. 7_Supplement (2023): 5935. http://dx.doi.org/10.1158/1538-7445.am2023-5935.

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Abstract Introduction: EGFR mutations holds the major targets for drug in lung adenocarcinoma (LUAD). Despite the tremendous study of EGFR mutant (MT) LUAD, the comprehensive interpretation of the heterogeneous character of LUAD harboring EGFR MT remains a key challenge. Here, we investigated the heterogeneity of EGFR MT LUAD and explored the tumor microenvironment (TME) in EGFR MT LUAD. Method: We performed single-cell RNA sequencing (scRNA-seq) from 135 LUAD patients which consist of normal(n=24), EGFR wild (WT)(n=18), and MT(n=93). Also, we used whole genome sequencing and bulk-RNA sequenci

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