Relevant bibliographies by topics / EGFR TKI

Contents

  1. Journal articles
  2. Dissertations / Theses
  3. Book chapters
  4. Conference papers
  5. Reports

Academic literature on the topic 'EGFR TKI'

Author: Grafiati
Published: 4 June 2021
Last updated: 25 May 2024

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'EGFR TKI.'

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.

Journal articles on the topic "EGFR TKI"

1

Simmons, Daniel, Maral DerSarkissian, Rahul Shenolikar, Min-Jung Wang, Angela Lax, Aruna Muthukumar, François Laliberté, and Mei Sheng Duh. "Real-world outcomes among patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors versus immunotherapy or chemotherapy in first-line setting." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19345-e19345. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19345.

Full text
Abstract:
e19345 Background: While epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are the NCCN-recommended first-line (1L) therapy for non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutation (EGFRm), many pts initiate immunotherapy (IO) + chemotherapy (chemo) prior to receiving EGFRm test results. This study assessed clinical outcomes associated with initiating EGFR-TKI vs other therapies in stage IV EGFRm NSCLC. Methods: A retrospective study was conducted in adult pts with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using data from Flatiron Health. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis was used to assess the median duration of therapy (mDoT) and time to next therapy (mTTNT), as proxies for progression-free survival. Adjusted hazards ratios (HR) and 95% confidence intervals (CI) representing the effect of 1L therapy on the risk of discontinuing treatment or death (DoT) and risk of initiating second-line therapy or death (TTNT) were reported from multivariable Cox proportional hazards models controlling for differences in demographics, smoking history, histology, cancer stage, ECOG score, NCI index, and year of and time from diagnosis to 1L initiation, across treatment arms. Results: Among 593 study pts, mean age was 67.5 years and 65.4% were female. EGFR-TKI was used as 1L therapy for 77.2% of pts (n=458), IO in 13.3% (n=79) and chemo alone in 9.4% (n=56). 7.2% of EGFR-TKI pts, 54.4% of IO pts, and 57.1% of chemo pts initiated 1L before receiving EGFRm test results. Compared to pts on IO and chemo alone, pts on EGFR-TKI had longer mDoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo alone: 3.0 mo, p<0.01) and mTTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo alone: 4.0 mo, p<0.01). After adjustment, pts on EGFR-TKI vs pts on IO or chemo alone had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (see Table). Conclusions: A substantial number of stage IV EGFRm NSCLC pts initiated IO or chemo alone in 1L and EGFR-TKI was associated with better clinical outcomes than IO or chemo alone, highlighting the importance of adhering to NCCN-recommended therapy for these pts. [Table: see text]
APA, Harvard, Vancouver, ISO, and other styles
2

Simmons, Daniel, Maral DerSarkissian, Rahul Shenolikar, Min-Jung Wang, Angela Lax, Aruna Muthukumar, François Laliberté, and Mei Sheng Duh. "Real-world outcomes among patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors versus immunotherapy or chemotherapy in first-line setting." Journal of Clinical Oncology 38, no. 29_suppl (October 10, 2020): 281. http://dx.doi.org/10.1200/jco.2020.38.29_suppl.281.

Full text
Abstract:
281 Background: While EGFR tyrosine kinase inhibitors (TKIs) are the NCCN-recommended first-line (1L) therapy for non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutation (EGFRm), many pts initiate immunotherapy (IO) + chemotherapy (chemo) prior to receiving EGFRm test results. This study assessed clinical outcomes associated with initiating EGFR-TKI vs other therapies in stage IV EGFRm NSCLC. Methods: A retrospective study was conducted in adults with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using Flatiron Health Electronic Health Record data. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis and log-rank tests were used to evaluate the median duration of therapy (DoT) and time to next therapy (TTNT), as proxies for progression-free survival. Adjusted hazards ratios (HR) and 95% confidence intervals (CI) representing the effect of 1L therapy on the risk of discontinuing treatment or death (DoT) and the risk of initiating second-line therapy or death (TTNT) were reported from multivariable Cox proportional hazards models controlling for differences in demographics, smoking history, histology, cancer stage, ECOG score, NCI index, time from diagnosis to 1L initiation, and year of 1L initiation, across treatment arms. Results: Among 593 study pts, mean age was 67.5 years and 65.4% were female. EGFR-TKI was used as 1L therapy for 77.2% of pts (n=458), IO in 13.3% (n=79) and chemo in 9.4% (n=56). 7.2% of EGFR-TKI pts, 54.4% of IO pts, and 57.1% of chemo pts initiated 1L before receiving EGFRm test results. Compared to pts on IO and chemo, pts on EGFR-TKI had longer median DoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo: 3.0 mo, p<0.01) and median TTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo: 4.0 mo, p<0.01). Adjusted analyses showed that compared to pts on IO or chemo, pts on EGFR-TKI had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (Table). Conclusions: Substantial numbers of pts initiated IO + chemo in 1L and EGFR-TKI was associated with better clinical outcomes than IO + chemo, suggesting the importance of adhering to NCCN-recommended therapy for stage IV EGFRm NSCLC pts. [Table: see text]
APA, Harvard, Vancouver, ISO, and other styles
3

Shenolikar, Rahul, Sizhu Liu, Jenny Tse, Yao Cao, and Aimee Near. "Real-world treatment patterns of metastatic non-small cell lung cancer (mNSCLC) patients receiving epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs)." Journal of Clinical Oncology 39, no. 28_suppl (October 1, 2021): 289. http://dx.doi.org/10.1200/jco.2020.39.28_suppl.289.

Full text
Abstract:
289 Background: Among mNSCLC patients positive for EGFR mutation (EGFRm), first-line (1L) treatment with an EGFR TKI is recommended for best outcomes. This study describes real-world treatment patterns of mNSCLC patients using EGFR TKIs in the 1L setting, including osimertinib, the most recently approved EGFR TKI for 1L use. Methods: Patients with ≥1 claim for an EGFR TKI (1st generation [1G]: gefitinib, erlotinib; 2nd generation [2G]: afatinib, dacomitinib; 3rd generation: osimertinib) from January 1, 2015 – April 30, 2020 were identified in IQVIA’s prescription (LRx) and medical claims (Dx) databases; first date of EGFR TKI was the index date. Patients had 12-month baseline period before index, variable follow-up after index, ≥1 lung cancer diagnosis on index or in baseline, and earliest metastatic cancer diagnosis on or 90 days before index. Kaplan-Meier analysis was used to estimate 1L treatment duration, where treatment discontinuation was defined as >60-day gap in medication supply of the index EGFR TKI. Patient characteristics and treatment patterns were stratified by 1L EGFR TKI. Results: Overall, 2,505 mNSCLC patients received 1L EGFR TKI (982 osimertinib, 1,060 1G, 463 2G). Median ages were 66-69 years, 64.6-67.1% were female, and 32.4-38.9% had central nervous system metastases on or before index. Most patients were commercially insured (50.8-62.9%), 35.3-45.9% had Medicare, and 0.6-3.3% had other payer types. Nearly all patients had 1L EGFR TKI monotherapy (97.6-99.7%). 1L treatment duration was longer for osimertinib compared to 1G or 2G EGFR TKI (median months, 17.8, 8.7, 10.5 respectively). 2L treatment was observed in 32.5% of 1G and 36.3% of 2G EGFR TKI cohorts. Osimertinib monotherapy, chemotherapy, and immunotherapy (monotherapy or combined with chemotherapy) accounted for 58.3%, 7.0%, and 4.3% of 2L treatments after 1L 1G EGFR TKI, respectively, and 60.7%, 4.2%, and 4.8% of 2L treatments after 1L 2G EGFR TKI. Conclusions: In real-world practice, 1L treatment duration is longer with osimertinib compared with other EGFR TKIs. Future studies with longer follow-up are recommended to understand treatment patterns after progression on EGFR TKIs, mainly osimertinib, given its recent approval.
APA, Harvard, Vancouver, ISO, and other styles
4

Ohmori, Tohru, Toshimitsu Yamaoka, Koichi Ando, Sojiro Kusumoto, Yasunari Kishino, Ryou Manabe, and Hironori Sagara. "Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury." International Journal of Molecular Sciences 22, no. 2 (January 14, 2021): 792. http://dx.doi.org/10.3390/ijms22020792.

Full text
Abstract:
The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and manageable, although serious AEs, including lung injury (specifically, interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, chronic obstructive pulmonary disease, and poor performance status, indicate that lung inflammatory circumstances may worsen with EGFR-TKI treatment because of impaired epithelial healing of lung injuries. There is limited evidence from preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced ILD in the available literature. Herein, we evaluated the relationship between EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung injury or resistance in cytokine-rich circumstances were reviewed. We discussed the relevance of cytotoxic agents or immunotherapeutic agents in combination with EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed recent developments in diagnostics and therapeutics that facilitate recovery from lung injury or overcoming resistance to anti-EGFR treatment.
APA, Harvard, Vancouver, ISO, and other styles
5

Urbanska, Edyta M., Morten Grauslund, Peter R. Koffeldt, Sarah L. B. Truelsen, Johan O. Löfgren, Junia C. Costa, Linea C. Melchior, Jens B. Sørensen, and Eric Santoni-Rugiu. "Real-World Data on Combined EGFR-TKI and Crizotinib Treatment for Acquired and De Novo MET Amplification in Patients with Metastatic EGFR-Mutated NSCLC." International Journal of Molecular Sciences 24, no. 17 (August 23, 2023): 13077. http://dx.doi.org/10.3390/ijms241713077.

Full text
Abstract:
Amplification of the mesenchymal epithelial transition (MET) gene is a mechanism of acquired resistance to epidermal growth factor receptor (EGFR)-tyrosine-kinase-inhibitors (TKIs) in over 20% of patients with advanced EGFR-mutated (EGFRm+) non-small lung cancer (NSCLC). However, it may also occur de novo in 2–8% of EGFRm+ NSCLC cases as a potential mechanism of intrinsic resistance. These patients represent a group with unmet needs, since there is no standard therapy currently approved. Several new MET inhibitors are being investigated in clinical trials, but the results are awaited. Meanwhile, as an alternative strategy, combinations of EGFR-TKIs with the MET/ALK/ROS1-TKI Crizotinib may be used in this setting, despite this use is principally off-label. Thus, we studied five of these MET amplified cases receiving EGFR-TKI and Crizotinib doublet after progression on EGFR-TKI treatment to assess the benefits and challenges related to this combination and the possible occurrence of genomic and phenotypic co-alterations. Furthermore, we compared our cases with other real-world reports on Crizotinib/EGFR-TKI combinations, which appeared effective, especially in patients with high-level MET amplification. Yet, we observed that the co-occurrence of other genomic and phenotypical alterations may affect the response to combined EGFR-TKI and Crizotinib. Finally, given the heterogeneity of MET amplification, the diagnostic methods for assessing it may be discrepant. In this respect, we observed that for optimal detection, immunohistochemistry, fluorescence in situ hybridization, and next-generation sequencing should be used together, as these methods possess different sensitivities and complement each other in characterizing MET amplification. Additionally, we addressed the issue of managing EGFR-mutated NSCLC patients with de novo MET amplification causing primary EGFR-TKI resistance. We conclude that, while data from clinical trials with new MET inhibitors are still pending, adding Crizotinib to EGFR-TKI in NSCLC patients acquiring MET amplification at progression on EGFR-TKI monotherapy is a reasonable approach, with a progression-free survival of 3–19 months.
APA, Harvard, Vancouver, ISO, and other styles
6

Santoni-Rugiu, Melchior, Urbanska, Jakobsen, Stricker, Grauslund, and Sørensen. "Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance." Cancers 11, no. 7 (July 1, 2019): 923. http://dx.doi.org/10.3390/cancers11070923.

Full text
Abstract:
Activating mutations in the epidermal growth factor receptor gene occur as early cancer-driving clonal events in a subset of patients with non-small cell lung cancer (NSCLC) and result in increased sensitivity to EGFR-tyrosine-kinase-inhibitors (EGFR-TKIs). Despite very frequent and often prolonged clinical response to EGFR-TKIs, virtually all advanced EGFR-mutated (EGFRM+) NSCLCs inevitably acquire resistance mechanisms and progress at some point during treatment. Additionally, 20–30% of patients do not respond or respond for a very short time (<3 months) because of intrinsic resistance. While several mechanisms of acquired EGFR-TKI-resistance have been determined by analyzing tumor specimens obtained at disease progression, the factors causing intrinsic TKI-resistance are less understood. However, recent comprehensive molecular-pathological profiling of advanced EGFRM+ NSCLC at baseline has illustrated the co-existence of multiple genetic, phenotypic, and functional mechanisms that may contribute to tumor progression and cause intrinsic TKI-resistance. Several of these mechanisms have been further corroborated by preclinical experiments. Intrinsic resistance can be caused by mechanisms inherent in EGFR or by EGFR-independent processes, including genetic, phenotypic or functional tumor changes. This comprehensive review describes the identified mechanisms connected with intrinsic EGFR-TKI-resistance and differences and similarities with acquired resistance and among clinically implemented EGFR-TKIs of different generations. Additionally, the review highlights the need for extensive pre-treatment molecular profiling of advanced NSCLC for identifying inherently TKI-resistant cases and designing potential combinatorial targeted strategies to treat them.
APA, Harvard, Vancouver, ISO, and other styles
7

Magnuson, William J., Nataniel H. Lester-Coll, Abraham J. Wu, T. Jonathan Yang, Natalie A. Lockney, Naamit K. Gerber, Kathryn Beal, et al. "Management of Brain Metastases in Tyrosine Kinase Inhibitor–Naïve Epidermal Growth Factor Receptor–Mutant Non–Small-Cell Lung Cancer: A Retrospective Multi-Institutional Analysis." Journal of Clinical Oncology 35, no. 10 (April 1, 2017): 1070–77. http://dx.doi.org/10.1200/jco.2016.69.7144.

Full text
Abstract:
Purpose Stereotactic radiosurgery (SRS), whole-brain radiotherapy (WBRT), and epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in patients with EGFR-mutant non–small-cell lung cancer (NSCLC). This multi-institutional analysis sought to determine the optimal management of patients with EGFR-mutant NSCLC who develop brain metastases and have not received EGFR-TKI. Materials and Methods A total of 351 patients from six institutions with EGFR-mutant NSCLC developed brain metastases and met inclusion criteria for the study. Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up. Patients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression. Overall survival (OS) and intracranial progression-free survival were measured from the date of brain metastases. Results The median OS for the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respectively ( P < .001). On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and absence of extracranial metastases were associated with improved OS. Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT cohort was more likely to have a less favorable prognosis ( P = .001). Conclusion This multi-institutional analysis demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with inferior OS in patients with EGFR-mutant NSCLC who develop brain metastases. SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to avoid the potential neurocognitive sequelae of WBRT. A prospective, multi-institutional randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgently needed.
APA, Harvard, Vancouver, ISO, and other styles
8

Yeo, Min-Kyung, Yoonjoo Kim, Da Hye Lee, Chaeuk Chung, and Go Eun Bae. "Cosuppression of NF-κB and AICDA Overcomes Acquired EGFR-TKI Resistance in Non-Small Cell Lung Cancer." Cancers 14, no. 12 (June 14, 2022): 2940. http://dx.doi.org/10.3390/cancers14122940.

Full text
Abstract:
Background: Acquired resistance after EGFR-tyrosine kinase inhibitor (TKI) treatment is the rule rather than the exception. Overcoming resistance to EGFR-TKIs is essential if we are to develop better therapeutic strategies for lung cancer patients. Here, we examine the effector signaling pathways underlying TKI resistance and propose targets to overcome the resistance of lung adenocarcinoma (LAC) to TKI. Methods: We compared the expression of NF-κB, AICDA, Akt, IL-6, Jak2, and Stat3 by EGFR-TKI-resistant and EGFR-TKI-sensitive LAC cell lines, and by LAC patients treated with EGFR-TKIs; we then evaluated links between expression and treatment responses. We also examined the therapeutic effects of NF-κB and AICDA inhibition in EGFR-TKI-resistant LACs. Results: NF-κB and AICDA were more expressed by EGFR-TKI-resistant LACs than by EGFR-TKI-sensitive LACs. EGFR-TKIs induced a dose-dependent increase in the expression of NF-κB, AICDA, and IL-6. Inhibition of NF-κB suppressed the expression of AICDA, Akt, and IL-6 in EGFR-TKI-resistant and EGFR-TKI-sensitive LACs, whereas knockdown of AICDA suppressed the expression of NF-κB and Akt in both cell types. Treating EGFR-TKI-resistant LACs with an EGFR-TKI, alongside cosuppression of NF-κB and AICDA, had a significant therapeutic effect. Conclusion: Treatment with an EGFR-TKI plus cosuppression of NF-κB and AICDA may be a promising strategy to overcome EGFR-TKI resistance in LACs.
APA, Harvard, Vancouver, ISO, and other styles
9

van de Stadt, Eveline Annette, Maqsood Yaqub, Robert C. Schuit, Imke H. Bartelink, Anke F. Leeuwerik, Lothar A. Schwarte, Adrianus J. de Langen, Harry Hendrikse, and Idris Bahce. "Relationship between Biodistribution and Tracer Kinetics of 11C-Erlotinib, 18F-Afatinib and 11C-Osimertinib and Image Quality Evaluation Using Pharmacokinetic/Pharmacodynamic Analysis in Advanced Stage Non-Small Cell Lung Cancer Patients." Diagnostics 12, no. 4 (April 1, 2022): 883. http://dx.doi.org/10.3390/diagnostics12040883.

Full text
Abstract:
Background: Patients with non-small cell lung cancer (NSCLC) driven by activating epidermal growth factor receptor (EGFR) mutations are best treated with therapies targeting EGFR, i.e., tyrosine kinase inhibitors (TKI). Radiolabeled EGFR-TKI and PET have been investigated to study EGFR-TKI kinetics and its potential role as biomarker of response in NSCLC patients with EGFR mutations (EGFRm). In this study we aimed to compare the biodistribution and kinetics of three different EGFR-TKI, i.e., 11C-erlotinib, 18F-afatinib and 11C-osimertinib. Methods: Data of three prospective studies and 1 ongoing study were re-analysed; data from thirteen patients (EGFRm) were included for 11C-erlotinib, seven patients for 18F-afatinib (EGFRm and EGFR wild type) and four patients for 11C-osimertinib (EGFRm). From dynamic and static scans, SUV and tumor-to-blood (TBR) values were derived for tumor, lung, spleen, liver, vertebra and, if possible, brain tissue. AUC values were calculated using dynamic time-activity-curves. Parent fraction, plasma-to-blood ratio and SUV values were derived from arterial blood data. Tumor-to-lung contrast was calculated, as well as (background) noise to assess image quality. Results: 11C-osimertinib showed the highest SUV and TBR (AUC) values in nearly all tissues. Spleen uptake was notably high for 11C-osimertinib and to a lesser extent for 18F-afatinib. For EGFRm, 11C-erlotinib and 18F-afatinib demonstrated the highest tumor-to-lung contrast, compared to an inverse contrast observed for 11C-osimertinib. Tumor-to-lung contrast and spleen uptake of the three TKI ranked accordingly to the expected lysosomal sequestration. Conclusion: Comparison of biodistribution and tracer kinetics showed that 11C-erlotinib and 18F-afatinib demonstrated the highest tumor-to-background contrast in EGFRm positive tumors. Image quality, based on contrast and noise analysis, was superior for 11C-erlotinib and 18F-afatinib (EGFRm) scans compared to 11C-osimertinib and 18F-afatinib (EGFR wild type) scans.
APA, Harvard, Vancouver, ISO, and other styles
10

Kawano, Yuko, Atsushi Horiike, Azusa Tanimoto, Toshio Sakatani, Ryota Saito, Kyohei Kaburaki, Noriko Yanagitani, et al. "Monitoring of plasma pro-GRP level during EGFR-TKI treatment." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 10604. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.10604.

Full text
Abstract:
10604 Background: Lung cancers harboring mutations in the epidermal growth factor receptor gene (EGFR) respond to EGFR tyrosine kinase inhibitors (EGFR-TKI), but drug resistance invariably emerges. The major acquired mechanisms of resistance are the EGFR T790M mutation or MET gene amplification. Transformation from NSCLC into small-cell lung cancer (SCLC) has been recently identified in acquired resistance to EGFR-TKI. However, it is difficult to predict the transformation during EGFR-TKI treatment because obtaining serial and sufficient specimens for biopsy is difficult. Pro-gastrin-releasing peptide (Pro-GRP) is a specific and sensitive tumor marker for SCLC. We evaluated the plasma Pro-GRP levels in EGFR-mutant NSCLCs and determined whether plasma Pro-GRP levels could predict SCLC transformation in resistance to EGFR-TKI. Methods: From July 2008 to December 2011, 49 patients with EGFR-mutant NSCLC who received EGFR-TKI treatment were enrolled. Plasma was obtained from these patients before EGFR-TKI treatment and when EGFR-TKI treatment failed. Pro-GRP and CEA levels were measured and compared before and after treatment. Results: Patient characteristics for 49 patients (15 men, 34 women) were as follows: median age, 62 years (41–81 years); histology, 46 adenocarcinomas (AD) and 3 non-AD tumors; and EGFR mutation type, 25 exon 19 deletions and 24 exon 21 L858R. All 49 patients had received EGFR-TKI treatment (45 with gefitinib and 4 with erlotinib); the response to EGFR-TKI treatment was PR in 39 patients, SD in 7, PD in 2, and NE in 1. Positive rate of ProGRP and CEA at pre-EGFR-TKI treatment was 2.0% and 57.2% and that at post-EGFR-TKI treatment was 6.1% and 69.4%, respectively. In 3 of 49 patients, the Pro-GRP levels had increased after treatment, but the CEA level did not increase. Objective responses to cytotoxic chemotherapy were noted in all 3 patients after EGFR-TKI treatment. Conclusions: Monitoring of plasma Pro-GRP during EGFR-TKI treatment may be useful for early detection of SCLC transformation in resistance to EGFR-TKI.
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "EGFR TKI"

1

Jeannot, Victor. "Identification et vectorisation de combinaisons de traitements pour la thérapie des tumeurs pulmonaires résistantes aux inhibiteurs de tyrosine kinase de l'EGFR." Thesis, Université Grenoble Alpes (ComUE), 2015. http://www.theses.fr/2015GREAV061/document.

Full text
Abstract:
Responsable d'environ 30000 décès/an en France, le cancer du poumon est un problème de santé publique majeur. Un des enjeux actuels est d'adapter le traitement du cancer du poumon pour proposer des thérapeutiques ciblées plus efficaces et moins agressives. Les inhibiteurs de l'activité tyrosine kinase du récepteur de l'EGF (EGFR-TKI, gefitinib et erlotinib) constituent un réel progrès pour le traitement des cancers du poumon. Cependant, des mécanismes de résistance ont été décrits et des traitements combinés de thérapies ciblées avec des EGFR-TKI pourraient permettre de surmonter les résistances dans les cancers du poumon.Dans ce contexte, nous avons étudié les mécanismes impliqués dans la résistance à ces traitements. Nous montrons que l'activation de la voie de signalisation PI3K/AKT joue un rôle majeur dans la résistance aux EGFR-TKI, en inhibant l'apoptose par des mécanismes dépendant de l'acétylation. Les histones déacétylases (HDACs) et les sirtuines interviennent dans ces mécanismes de résistance, en modulant l'activation de la voie PI3K/AKT et l'apoptose. Ainsi l'utilisation d'inhibiteurs des HDACs (HDACi) et des sirtuines permettent de restaurer la sensibilité aux EGFR-TKI. Ces résultats confirment l'intérêt thérapeutique de l'association EGFR-TKI/HDACi et montrent le potentiel thérapeutique d'associer des inhibiteurs de l'EGFR et de la voie PI3K/AKT pour contourner la résistance aux EGFR-TKI.Les molécules thérapeutiques doivent atteindre spécifiquement le site tumoral, nécessitant parfois de les protéger contre leur dégradation, de réduire leurs effets indésirables, et de contrôler leur libération dans le temps et l'espace, à l'aide de transporteurs. Ainsi dans la deuxième partie de cette thèse, nous avons évalué les capacités de ciblage des tumeurs pulmonaires de nanoparticules à base de copolymère amphiphile, contenant une partie polysaccharidique hydrophile (le hyaluronane) et une partie polypeptidique hydrophobe (le poly(γ‐benzyl L‐glutamate, PBLG). Nos travaux mettent en évidence la capacité de ciblage tumoral de ces nanoparticules injectées par voie intraveineuse, ouvrant ainsi de nouvelles perspectives thérapeutiques. Notre objectif est de charger les combinaisons de traitements EGFR-TKI/HDACi que nous avons identifiées dans ces vecteurs, afin de traiter les tumeurs pulmonaires résistantes aux EGFR-TKI
Responsible of 30000 deaths each year in France, lung cancer is a major public health problem. One of the current challenges is to adapt the treatment of lung cancer to offer more effective and less aggressive targeted therapies. EGFR tyrosine kinase inhibitors (EGFR-TKI, gefitinib and erlotinib) represent a real progress in lung cancer therapy. However resistance mechanisms have been described and combination of targeted therapy with EGFR-TKI could overcome resistance in lung cancer.In this context, we studied mechanisms involved in resistance to EGFR-TKI. We show that PI3K/AKT activation is a major pathway leading to EGFR-TKI resistance leading to apoptosis inhibition through acetylation-dependent mechanisms. Histone deacetylase (HADCs) and sirtuin are involved in these mechanisms and modulate PI3K/AKT activation and apoptosis. The use of HDACs inhibitors (HDACi) and sirtuins inhibitors thus restores the sensitivity to EGFR-TKI. Altogether these results confirm the therapeutic effect of the EGFR-TKI/HDACi combination and show the therapeutic potential of the association of EGFR and PI3K/AKT inhibitors to overcome EGFR-TKI resistance.Therapeutic molecules must specifically reach the tumor site, sometimes requiring to protect them against degradation, to reduce their side effects, and to control their release in time and space, using transporters. In the second part of this thesis, we have thus evaluated the lung tumors targeting capabilities of amphiphilic copolymer-based nanoparticles, containing an hydrophilic polysaccharidic block (hyaluronan) and an hydrophobic polypeptidic block (the poly(γ‐benzyl L‐glutamate PBLG). Our work highlights the tumor targeting capability of these nanoparticles injected intravenously, offering new lung cancer therapy perspectives. Our aim is to load the drugs combination (EGFR-TKI/HDACi) in these vectors, to treat the lung tumors resistant to EGFR-TKI
APA, Harvard, Vancouver, ISO, and other styles
2

Guérard, Marie. "Signalisation nucléaire de l'IGF-1R et résistance aux thérapies anti-EGFR dans les cancers du poumon." Thesis, Université Grenoble Alpes (ComUE), 2016. http://www.theses.fr/2016GREAV085/document.

Full text
Abstract:
Responsable de 1,6 million de décès par an dans le monde, le cancer du poumon constitue aujourd’hui la première cause de mortalité par cancer. Les cancers bronchiques non-à-petites cellules représentent 85% des cancers du poumon et ont un pronostic vital très mauvais. Les EGFR-TKI (inhibiteurs de l’activité tyrosine kinase de l’EGFR, gefitinib) constituent un réel progrès thérapeutique pour le traitement des cancers du poumon. Cependant, ces traitements ne sont efficaces que dans un petit sous-groupe de patients. Un des enjeux actuels est donc d’identifier les mécanismes de résistance primaire mis en jeu par les tumeurs.Les récepteurs à activité tyrosine kinase (RTK) activent des voies de signalisation intracellulaires depuis la membrane plasmique. Ces dernières années, une translocation nucléaire des RTK a également été mise en évidence. Ces travaux récents suggèrent que la signalisation nucléaire des RTK pourrait contribuer à la résistance des tumeurs en réponse aux thérapies anti-cancéreuses.Dans l’équipe, il a été montré que l’activation de l’IGF-1R est associée à la progression tumorale des adénocarcinomes pulmonaires et que le gefitinib induit une accumulation nucléaire de l’IGF-1R dans un modèle d’adénocarcinome mucineux. Sur la base de ces résultats, nous avons émis l’hypothèse que l’IGF-1R nucléaire pourrait jouer un rôle dans la résistance aux EGFR-TKI des adénocarcinomes pulmonaires mucineux.Nos résultats indiquent que plus de 70% des adénocarcinomes pulmonaires présentent un marquage nucléaire de l’IGF-1R. A l’aide de différents modèles cellulaires résistants aux EGFR-TKI, nous montrons que le gefitinib induit l’accumulation nucléaire de l’IGF-1R dans les adénocarcinomes pulmonaires mucineux. Cette translocation nucléaire implique l’endocytose clathrines-dépendante de l’IGF-1R et la formation d’un complexe entre l’IGF-1R, l’importine β1 et la pro-amphiréguline. La neutralisation de l’amphiréguline prévient le transport nucléaire de l’IGF-1R et resensibilise les cellules à l’apoptose induite par le gefitinib in vitro et in vivo. L’ensemble de ces résultats identifient le trafic intracellulaire de l’IGF-1R comme un nouveau composant de la réponse aux EGFR-TKI et suggèrent que la signalisation nucléaire IGF-1R/Areg contribue à la progression des adénocarcinomes mucineux sous EGFR-TKI
Responsible of 1.6 million deaths each year worldwide, lung cancer is today the leading cause of cancer mortality in the world. Non-small-cell lung cancers account for about 85% of lung cancer and have a very bad prognosis (5-year survival rate inferior to 10%). EGFR-TKI (EGFR tyrosine kinase inhibitors, gefitinib) are a real medical advance for lung cancers treatment. However, these treatments are efficient in a small subgroup of patients. So, one of the current issues is to identify primary resistance mechanisms involved in tumors.Tyrosine kinase receptors (RTK) activate intracellular signaling pathways from the plasma membrane. These last years, a nuclear translocation of the RTK was shown. Recent works suggest that RTK nuclear signaling could contribute to tumors resistance in response to anti-cancerous therapies.In our team, it was shown that activation of IGF-1R signaling is associated with lung adenocarcinoma progression and that gefitinib induces IGF-1R nuclear accumulation in a mucinous adenocarcinoma cell line. On the basis of these results, we hypothesize that nuclear IGF-1R could play a role in the resistance of mucinous lung adenocarcinoma to EGFR-TKI.Our results indicate that more than 70% lung adenocarcinoma tumors present a positive IGF-1R nuclear staining. Thanks to EGFR-TKI-resistant cell lines, we show that gefitinib induces the nuclear accumulation of IGF-1R in mucinous adenocarcinoma. This nuclear translocation involves clathrin-mediated endocytosis and a complex between IGF-1R, importin β1 and pro-amphiregulin. Amphiregulin silencing prevents IGF-1R nuclear translocation in response to gefitinib and restores gefitinib-induced apoptosis in vitro and in vivo. Our whole results identify that IGF-1R intracellular trafficking is a new component of response to EGFR-TKI and strongly suggest that a nuclear IGF-1R/amphiregulin signaling contributes to mucinous lung adenocarcinoma progression in response to EGFR-TKI
APA, Harvard, Vancouver, ISO, and other styles
3

Martinsson, Caroline. "Characterisation of EGFR and KRAS mutations in non-small cell lung cancer." Thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-126041.

Full text
Abstract:
Background: Lung cancer is the leading cause of cancer-related death and one of the most common cancer types worldwide. Epidermal growth factor receptor (EGFR) has been shown to be an important therapeutic target in non-small cell lung cancer. Kirsten rat sarcoma viral oncogene homologue (KRAS) is a downstream signalling molecule in the EGFR pathway. Lung cancer patients with EGFR mutations respond to tyrosine EGFR inhibitor therapy, in contrast, patients with KRAS mutations do not benefit of such treatment. Methods: This study investigates the frequency of EGFR and KRAS mutations in non-small cell lung cancer patients. Fifty-one lung cancer patients with primary non-small cell lung cancer diagnosed between 1995 and 2005 in the Uppsala-Örebro region were analysed by Sanger sequencing and Pyrosequencing to determine the mutation status of these genes. Results: Five EGFR mutations were found in four patients (8%), two deletions in exon 19, one point mutation in exon 20 and two point mutations in exon 21. KRAS mutations were found in 12 patients (24%), ten codon 12 mutations and two codon 61 mutations. Conclusions: This study confirms previous observations regarding the frequency of EGFR and KRAS mutations in non-small cell lung cancer. Mutations in EGFR and KRAS were mutually exclusive, indicating that both mutations present relevant tumorigenic genomic aberrations.
APA, Harvard, Vancouver, ISO, and other styles
4

Yang, Zheng. "Anti-cancer synergy of targeting pyruvate dehydrogenase kinase 1 (PDK1) in combination with EGFR-TKi in NSCLC therapy." Thesis, University of Macau, 2018. http://umaclib3.umac.mo/record=b3953612.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Brand, Thomas. "Studio della correlazione fra la percentuale di cellule neoplastiche mutate in EGFR e la risposta a farmaci TKI nell'adenocarcinoma polmonare." Bachelor's thesis, Alma Mater Studiorum - Università di Bologna, 2016. http://amslaurea.unibo.it/11148/.

Full text
Abstract:
Il gene EGFR e' un marcatore molecolare fondamentale per determinare la sensibilita' o meno ai farmaci inibitori delle tirosin-chinasi (TKI) in pazienti affetti da adenocarcinoma polmonare. Lo scopo del lavoro e' di determinare se la percentuale di cellule neoplastiche mutate in EGFR correli con la risposta ai farmaci TKI. Sono stati analizzati 18 casi; di ogni caso e' stato analizzato il gene EGFR (esoni 18, 19, 20 e 21) mediante Next Generation Sequencing (NGS). La quantita' di cellule neoplastiche presenti nell'area analizzata e' stata valutata da un patologo, su un vetrino colorato con Ematossilina-Eosina, e tale quantita' e' stata normalizzata alla percentuale di alleli mutati rilevata mediante NGS. E' stata rilevata una correlazione fra la percentuale di cellule neoplastiche mutate in EGFR e la risposta ai TKI, ed e' stato osservato che pazienti con una percentuale di cellule neoplastiche mutate al di sopra del 56% presentano una migliore "overall survival" rispetto ai pazienti con una percentuale inferiore. I dati suggeriscono che, oltre al valore predittivo, la definizione della percentuale di cellule neoplastiche mutate in EGFR potrebbe avere un valore prognostico.
APA, Harvard, Vancouver, ISO, and other styles
6

Choi, Ho-ying, and 蔡可盈. "Review of clinical benefits and cost effectiveness of epidermal growthfactor receptor-tyrosine kinase inhibitor (EGFR-TKI) as first linetreatment for patients with advanced non-small cell lung cancer(NSCLC)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B46935320.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Castelain, Lauriane. "Sphingosine kinase 1, transition épithélio-mésenchymateuse et résistance primaire aux inhibiteurs pharmacologiques de l'EGFR." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066595.

Full text
Abstract:
Une transition épithélio-mésenchymateuse (TEM) et une expression élevée de la sphingosine kinase 1 (SPHK1) sont souvent observées dans les cancers. Notre étude du génome et du transcriptome d'adénocarcinomes pulmonaires (AP) montre que l'expression élevée de SPHK1 est en rapport, d'une part, avec des gains de la région incluant le locus SPHK1 et, d'autre part, avec une signature d'expression génique de TEM dans des tumeurs invasives. L'expression de SPHK1 est restreinte aux cellules tumorales. La surexpression de SPHK1 dans des cellules d'AP et l'exposition à son produit, la sphingosine-1-phosphate (S1P), entraînent une TEM, de manière réversible pour la S1P. La surexpression de SPHK1 active aussi NF-kB. La surexpression du facteur anti-apoptotique FLIP active NF-kB, induit une TEM et augmente l'expression de SPHK1, suggérant une boucle d'amplification entre NF-kB et SPHK1. Une TEM et la surexpression de FLIP ont été impliquées dans la résistance primaire aux inhibiteurs pharmacologiques de l'EGFR (EGFR TKI). Nous montrons que la surexpression de SPHK1 dans des cellules A549 diminue modestement la sensibilité au gefitinib, alors que l'inhibition de SPHK1 ou la déplétion du sérum en S1P l'augmentent modestement. L'invalidation de SPHK1 entraîne l'apoptose d'A549 y compris quand FLIP est surexprimé. L'activation et le maintien d'une TEM sont généralement attribués à des signaux contextuels du stroma. Cette thèse montre que les cellules tumorales elles-mêmes favorisent la surexpression de SPHK1 qui peut induire une TEM de façon autonome. De plus, la surexpression de FLIP impliquée dans la résistance aux EGFR TKI, n'empêche pas l'apoptose induite par l'invalidation de SPHK1
Epithelial-mesenchymal transition (EMT) and sphingosine kinase 1 (SPHK1) high expression are often seen in cancers. Our study of genomic and gene expression data in pulmonary adenocarcinomas (AP) shows that SPHK1 high expression correlates with both gains in the region encompassing the SPHK1 locus, and an EMT gene expression signature in invasive tumors. SPHK1 expression is restricted to tumors cells. SPHK1 overexpression in AP cells, as well as exposure to its productsphingosine-1-phosphate (S1P),induce an EMT -in a reversible manner for S1P. SPHK1 overexpression also activates NF-kB. Overexpression of FLIP – an antiapoptotic factor - activates NF-kB, induces an EMT, and increases SPHK1 expression, suggesting an amplification loop between NF-kB and SPHK1. EMT and FLIP overexpression are known to favor primary resistance to EGFR pharmacological inhibitors (EGFR TKI). We show that SPHK1 overexpression in A549 cells slightly decreases cell sensitivity to gefitinib, while pharmacologic inhibition of SPHK1 or serum S1P depletionincrease it. Downregulation of SPHK1 expression induces apoptosis of A549 cells even when FLIP is overexpressed. Activation and maintenance of EMT are generally attributed to contextual signals from the stroma. Here, we show that tumor cells themselves favor SPHK1 overexpression, which can led to EMT in cell-autonomous manner. In addition, FLIP overexpression which is implicated in EGFR TKI resistance, cannot prevent apoptosis that is induced by SPHK1 invalidation
APA, Harvard, Vancouver, ISO, and other styles
8

Sahin, Katherine B. "Evaluation of cell division cycle associated protein 3 (CDCA3) as a novel prognostic/therapeutic target for EGFR-mutant non-small cell lung cancer." Thesis, Queensland University of Technology, 2022. https://eprints.qut.edu.au/231468/1/Katherine_Sahin_Thesis.pdf.

Full text
Abstract:
This thesis defined a unique role for the protein cell division cycle associated protein-3 (CDCA3) in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). This thesis has established an association between the levels of CDCA3 expression and the tumour response to tyrosine kinase inhibitors (TKI), which are the front-line therapy for EGFR-mutant NSCLC. In this disease, CDCA3 functions to modulate cellular growth pathways to impact sensitivity towards TKI therapy. Future work might enable development of a clinical stratification tool to discern TKI responsive from non-responsive EGFR-mutant NSCLC tumours.
APA, Harvard, Vancouver, ISO, and other styles
9

Costa, Daniel Botelho. "Determinantes moleculares de resposta e resistencia aos inibidores da tirosina quinase (TKI) em pacientes com carcinoma de pulmão não pequenas celulas (CPNPC) com mutações no gene do recptor do fator de crescimento epidermico (EGFR)." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/308123.

Full text
Abstract:
Orientador: Lair Zambon
Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-12T08:23:12Z (GMT). No. of bitstreams: 1 Costa_DanielBotelho_D.pdf: 9890444 bytes, checksum: 90e3892529ddea892b184c2ca660ac69 (MD5) Previous issue date: 2008
Resumo: A maioria dos carcinomas de pulmão não pequenas células (CPNPC) em estádios avançados com mutações ativadoras (deleções do exon 19 ou a mutação L858R do exon 21) do receptor do fator de crescimento epidérmico (EGFR) respondem inicialmente, aos medicamentos gefitinib e erlotinib, que são inibidores da tirosina quinase (TKIs) do EGFR. Porém em uma média de 6-12, meses esses tumores desenvolvem resistência adquirida aos TKIs do EGFR. Dois mecanismos de resistência ao gefitinib/erlotinib explicam porque os CPNPC com mutações do EGFR se tornam resistentes aos TKIs: mutações de resistência secundária e um sistema de "troca de oncogenes". A mutação T790M-EGFR secundária ocorre em 50% dos pacientes com mutação no EGFR com resistência adquirida aos TKIs do EGFR, e em in vitro esta mutação T790M-EGFR inativa a hipersensitividade das mutações ativadoras do EGFR ao gefitnib ou erlotinib. Outras mutações de resistência secundárias (D761Y, L747S, A854T) são raras. Um outro mecanismo de resistência é a amplificação adquirida do oncogene MET, que ocorre em mais ou menos 20% do pacientes resistentes ao gefitinib/erlotinib e, em metade destes casos, em conjunção com T790M. O MET ativa sinais de sinalização que contornam o EGFR inibido, gerando um sistema de "troca de oncogenes" nesses tumores. Esses dados pré-clinicos relevantes aos CPNPCs com o EGFR mutado e resistência ao gefitinib ou erlotinib levaram ao desenvolvimento de experimentos clínicos com novos inibidores do EGFR que inibem "in vitro" a mutação T790M-EGFR (HKI-272, XL-647, BIBW-2992 e PF00299804), e inibidores de MET mais TKIs do EGFR em combinação. Neste trabalho: 1) Agrupamos e resumimos os dados dos experimentos clínicos prospectivos com o gefinitib em pacientes com o EGFR mutado. Mais de 80% dos pacientes com deleções do exon 19 ou a mutação L858R do EGFR tiveram resposta radiográfica, com sobrevivência livre de progressão de 7,7 a 12,9 meses nos estudos identificados, e sobrevivência geral acima de 15 meses; 2) Usamos células CPNPC com mutações do EGFR para identificarmos a molécula pró-apoptótica BIM como o efetor principal da apoptose induzida pelos TKIs do EGFR; 3) Caracterizamos a mutação resistente ao gefinitib EGFR-L858R-L747S, e determinamos que L858R-L747S apresenta um padrão de resistência menos acentuado ao gefitinib do que o observado com L858R-T790M; e 4) Avaliamos os efeitos do erlotinib em pacientes com CPNPC EGFR mutado e resistência ao gefitinib, caracterizando a correlação da resposta radiográfica e clínica com os mecanismos conhecidos de resistência ao TKIs do EGFR (as mutações de resistência secundárias T790M e L747S, e a amplificação do MET). A maioria (mais de 83%) dos pacientes resistentes ao gefitinib tiveram progressões radiográficas nos primeiros 2 a 4 meses de exposição ao erlotinib 150 mg/dia. Isto é consistente com nossas observações pré-clínicas, indicativas de que a maioria dos tumores resistentes ao gefitinib possui predominantemente T790M e/ou amplificações do MET, que são resistentes tanto ao gefitinib quanto erlotinib. Pesquisas pré-clínicas e experimentos clínicos futuros do CPNPC com EGFR mutado têm o potencial de melhorar os resultados do tratamento clínico de pacientes com essas mutações somáticas.
Abstract: Most advanced non-small cell lung cancers (NSCLCs) with activating epidermal growth factor receptor (EGFR) mutations (exon 19 deletions or L858R) initially respond to the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. However, over time (median of 6-12 months) most tumors develop acquired resistance to EGFR TKIs. Intense research in these NSCLCs has identified two major mechanisms of resistance to gefitinib/erlotinib: secondary resistance mutations and "oncogene kinase switch" systems. The secondary T790M mutation occurs in 50% of EGFR mutated patients with TKI resistance, and in vitro this mutation negates the hypersensitivity of activating EGFR mutations. Other secondary resistance mutations (D761Y, L747S, A854T) seem to be rare. The amplification of the MET oncogene is present in 20% of TKI-resistant tumors; however in half of the cases with this "oncogene kinase switch" mechanism the T790M is co-existent. The growing pre-clinical data in EGFR mutated NSCLCs with acquired resistance to gefitinib or erlotinib has spawned the initiation or conception of clinical trials testing novel EGFR inhibitors that in vitro inhibit T790M (HKI-272, XL-647, BIBW-2992 and PF00299804), and MET inhibitors in combination with EGFR TKIs. In this work we: 1) Pooled and summarized data from prospective clinical trials of gefitinib for EGFR mutated patients. More than 80% of patients with exon 19 deletions or the L858R EGFR mutation attained a radiographic response with progression-free survival of 7.7 to 12.9 months in the identified studies, and overall survival exceeding 15 months; 2) Identified the pro-apoptotic molecule BIM as the main effector of EGFR TKI-induced apoptosis using NSCLC cell lines with EGFR mutations; 3) Characterized the L858R-L747S gefitinib-resistant mutation, and demonstrated that L858R-L747S has a partial resistance pattern when compared to L858R-T790M; and 4) Evaluated the effects of erlotinib in EGFR mutated NSCLC with resistance to gefitinib while characterizing the correlation of response and resistance to this approach to the known mechanisms of resistance to EGFR TKIs (the secondary mutations T790M and L747S, and the amplification of MET). Our clinical observation was that the majority (over 83%) of the gefitinib-resistant patients given erlotinib 150 mg/day had radiographic progression within the first 2 to 4 months of exposure. This is consistent with our pre-clinical observations, since we expected gefitinib-resistant tumors to predominantly harbor T790M and/or MET amplification, which are cross-resistant to both gefitinib and erlotinib. Ongoing pre-clinical and clinical research in EGFR mutated NSCLC has the potential to significantly improve the outcomes of patients with these somatic mutations.
Doutorado
Clinica Medica
Doutor em Clínica Médica
APA, Harvard, Vancouver, ISO, and other styles
10

Castelain, Lauriane. "Sphingosine kinase 1, transition épithélio-mésenchymateuse et résistance primaire aux inhibiteurs pharmacologiques de l'EGFR." Electronic Thesis or Diss., Paris 6, 2016. http://www.theses.fr/2016PA066595.

Full text
Abstract:
Une transition épithélio-mésenchymateuse (TEM) et une expression élevée de la sphingosine kinase 1 (SPHK1) sont souvent observées dans les cancers. Notre étude du génome et du transcriptome d'adénocarcinomes pulmonaires (AP) montre que l'expression élevée de SPHK1 est en rapport, d'une part, avec des gains de la région incluant le locus SPHK1 et, d'autre part, avec une signature d'expression génique de TEM dans des tumeurs invasives. L'expression de SPHK1 est restreinte aux cellules tumorales. La surexpression de SPHK1 dans des cellules d'AP et l'exposition à son produit, la sphingosine-1-phosphate (S1P), entraînent une TEM, de manière réversible pour la S1P. La surexpression de SPHK1 active aussi NF-kB. La surexpression du facteur anti-apoptotique FLIP active NF-kB, induit une TEM et augmente l'expression de SPHK1, suggérant une boucle d'amplification entre NF-kB et SPHK1. Une TEM et la surexpression de FLIP ont été impliquées dans la résistance primaire aux inhibiteurs pharmacologiques de l'EGFR (EGFR TKI). Nous montrons que la surexpression de SPHK1 dans des cellules A549 diminue modestement la sensibilité au gefitinib, alors que l'inhibition de SPHK1 ou la déplétion du sérum en S1P l'augmentent modestement. L'invalidation de SPHK1 entraîne l'apoptose d'A549 y compris quand FLIP est surexprimé. L'activation et le maintien d'une TEM sont généralement attribués à des signaux contextuels du stroma. Cette thèse montre que les cellules tumorales elles-mêmes favorisent la surexpression de SPHK1 qui peut induire une TEM de façon autonome. De plus, la surexpression de FLIP impliquée dans la résistance aux EGFR TKI, n'empêche pas l'apoptose induite par l'invalidation de SPHK1
Epithelial-mesenchymal transition (EMT) and sphingosine kinase 1 (SPHK1) high expression are often seen in cancers. Our study of genomic and gene expression data in pulmonary adenocarcinomas (AP) shows that SPHK1 high expression correlates with both gains in the region encompassing the SPHK1 locus, and an EMT gene expression signature in invasive tumors. SPHK1 expression is restricted to tumors cells. SPHK1 overexpression in AP cells, as well as exposure to its productsphingosine-1-phosphate (S1P),induce an EMT -in a reversible manner for S1P. SPHK1 overexpression also activates NF-kB. Overexpression of FLIP – an antiapoptotic factor - activates NF-kB, induces an EMT, and increases SPHK1 expression, suggesting an amplification loop between NF-kB and SPHK1. EMT and FLIP overexpression are known to favor primary resistance to EGFR pharmacological inhibitors (EGFR TKI). We show that SPHK1 overexpression in A549 cells slightly decreases cell sensitivity to gefitinib, while pharmacologic inhibition of SPHK1 or serum S1P depletionincrease it. Downregulation of SPHK1 expression induces apoptosis of A549 cells even when FLIP is overexpressed. Activation and maintenance of EMT are generally attributed to contextual signals from the stroma. Here, we show that tumor cells themselves favor SPHK1 overexpression, which can led to EMT in cell-autonomous manner. In addition, FLIP overexpression which is implicated in EGFR TKI resistance, cannot prevent apoptosis that is induced by SPHK1 invalidation
APA, Harvard, Vancouver, ISO, and other styles
More sources

Book chapters on the topic "EGFR TKI"

1

Cappuzzo, Federico. "Overcoming EGFR-TKI Resistance." In Guide to Targeted Therapies: Treatment Resistance in Lung Cancer, 37–50. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20741-4_4.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Cappuzzo, Federico. "Resistance to EGFR TKIs." In Guide to Targeted Therapies: Treatment Resistance in Lung Cancer, 27–36. Cham: Springer International Publishing, 2015. http://dx.doi.org/10.1007/978-3-319-20741-4_3.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Arslan, Serap. "Akciğer Kanserinde Güncel Genetik Algoritma ve Tedavi Seçenekleri." In Kanserlere Yeni Hedefli Terapötik Yaklaşımlar. Özgür Yayınları, 2023. http://dx.doi.org/10.58830/ozgur.pub80.c247.

Full text
Abstract:
Kanserin moleküler özelliklerinin anlaşılmaya başlamasıyla birlikte çalışmalar hedefe yönelik tedaviler üzerine yoğunlaşmıştır. Akciğer kanseri ile ilgili yapılan hücresel ve moleküler mekanizma çalışmaları sayesinde hastalığın epidemiyolojisi, prognozu, tanı ve tedavisinde önemli ilerlemeler kaydedilmiştir. Akciğer kanseri dünyada %11,4 insidans ve %18 mortalite oranıyla en yaygın görülen kanser tiplerinden biridir. Akciğer kanseri etiyolojisinde sigara, yaş, ırk, cinsiyet, meslek, hava kirliliği, radyasyon, genetik ve immünolojik faktörler de etiyolojik faktörler arasında yer almaktadır. Akciğer kanseri biyolojisi, tedavisi ve prognozuna göre başlıca küçük hücreli (%15) ve küçük hücreli dışı (%85) olmak üzere iki ana sınıfa ayrılır. Akciğer kanseri gelişiminde onkogenlerin aktivasyonu ve tümör baskılayıcı genlerin inaktivasyonu en önemli genetik etkendir. Akciğer adenokarsinomlarında günümüzde kullanılan onaylı ajanlarla hedeflenebilir değişiklikler, EGFR, ALK, BRAF, RET, NTRK1-2-3, ROS1, MET, ERRB2 ve KRAS gibi genlerdeki nokta mutasyonları, in-frame delesyonlar, splice varyantları ve translokasyonları içerir. NCCN KHDAK Paneli, metastatik KHDAK'li uygun hastalar için moleküler testler önermektedir. Klinik kılavuzlar tüm ileri evre veya metastatik akciğer adenokarsinomlarında EGFR-ALK-ROS panelinin klinisyen tarafından istenmesi gerektiğini vurgulamaktadır. Hedefe yönelik tedavi alan olgularda sağ kalım oranı daha uzundur. Özellikle EGFR E19 del, L858R mutasyonu, ALK ve ROS yeniden düzenlenmelerinde TKI karşı yanıt söz konusudur. Tedavi sonrası hastalarda direnç gelişebilir. Hedefe yönelik tedavilerde bu direnç mekanizmaları karşı terapötik ajan geliştirme üzerine birçok umut vaat eden çalışma devam etmektedir. Çalışmalardan elde edilen veriler arttıkça gelecekte kişiye özel alternatif tedavi seçenekleri de karşımıza çıkacaktır.
APA, Harvard, Vancouver, ISO, and other styles
4

Xi, Jiyu, Zewen Wei, Xin Wu, Kexin Zhang, Huiting Zhao, and Yu Zhang. "Dual-Function Microfluidic Chip for Identification and Drug Response Testing of Lung Cancer Organoids." In Fuzzy Systems and Data Mining IX. IOS Press, 2023. http://dx.doi.org/10.3233/faia231106.

Full text
Abstract:
Organoids, as a novel in vitro drug screening platform, have received widespread attention due to their relevance to clinical research as they are derived from patient samples. Lung cancer organoids are categorized into two subtypes: EGFR mutation type and EGFR wild type. EGFR mutation lung cancer organoids exhibit better therapeutic effects with tyrosine kinase inhibitors (TKIs), whereas EGFR wild type lung cancer organoids have better responses to chemotherapy drugs. However, the current lack of a microfluidic chip capable of identifying EGFR mutations in lung cancer organoids and testing their drug response poses a challenge. To address this, we have developed a dual-functional chip that streamlines EGFR mutation identification and drug testing in lung cancer organoids. This method not only reduces time and cost but also enhances drug screening efficiency.
APA, Harvard, Vancouver, ISO, and other styles
5

Adachi, Yuta, and Hiromichi Ebi. "Role of epithelial to mesenchymal transition in the resistant mechanism of EGFR-TKIs." In Overcoming Resistance to EGFR Inhibitors in EGFR Mutant NSCLC, 55–70. Elsevier, 2023. http://dx.doi.org/10.1016/b978-0-12-822833-3.00005-x.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Hirsh, Vera. "Adverse Effects Induced by EGFR-TKIs: Rash and Diarrhea — Their Management." In Modern Thoracic Oncology, 223–31. WORLD SCIENTIFIC, 2018. http://dx.doi.org/10.1142/9789813236318_0021.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Conference papers on the topic "EGFR TKI"

1

Lee, An-Chun, Chia-Cherng Yu, Yuan-Hung Wang, and Yu-Ting Chou. "Abstract 5906: EGFR and SOX2 crosstalk determines EGFR-TKI." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-5906.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Raimbourg, Judith, Mathilde Cabart, Marie-Pierre Joalland, Didier Decaudin, Ludmilla Deplater, Didier Lanoe, Jean-Yves Douillard, Jaafar Bennouna, François Vallette, and Lisenn Lalier. "Abstract 2559: Optimisation of EGFR TKI efficiency wild-type EGFR lung cancer." In Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1538-7445.am2015-2559.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Koba, Hayato, Hideharu Kimura, Shingo Nishikawa, Taro Yoneda, Takashi Sone, and Kazuo Kasahara. "Abstract 2268: Detection of T790M mutation in EGFR gene, an EGFR-TKI resistant mutation, in tumor samples unexposed to EGFR TKIs." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2268.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Osude, Chike, Leo Lin, and Neelu Puri. "Abstract 189: EGFR TKI resistance via role VEGFR2." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.sabcs18-189.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

Osude, Chike, Leo Lin, and Neelu Puri. "Abstract 189: EGFR TKI resistance via role VEGFR2." In Proceedings: AACR Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1538-7445.am2019-189.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Osoegawa, Atsushi, Tomonori Yamada, Takafumi Hashimoto, Yohei Takumi, Ryoji Kobayashi, Shuji Suehiro, Michiyo Miyawaki, Hideya Takeuchi, Tatsuro Okamoto, and Kenji Sugio. "Abstract 4107: Acquired resistance to EGFR-TKI in an uncommon G719S EGFR mutation." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-4107.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Simone Clement, Michelle, Boe Sandahl Sorensen, Sinead Cuffe, Stephen Finn, and Kathy Gately. "Targeting STAT3 pathway signalling in EGFR TKI resistant NSCLC." In ERS International Congress 2020 abstracts. European Respiratory Society, 2020. http://dx.doi.org/10.1183/13993003.congress-2020.330.

Full text
APA, Harvard, Vancouver, ISO, and other styles
8

Dooper, Marten. "Adding chemotherapy to EGFR TKI does not improve OS in advanced EGFR-mutated NSCLC." In ASCO Annual Meeting 2023, edited by Stefan Rauh. Baarn, the Netherlands: Medicom Medical Publishers, 2023. http://dx.doi.org/10.55788/f86232d3.

Full text
APA, Harvard, Vancouver, ISO, and other styles
9

Kimura, Hideharu, Makoto Nishio, Tsutomu Daito, and Kazuto Nishio. "Abstract 557: Noninvasive analysis of acquired resistance to EGFR-TKI." In Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-557.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Wei, Rongrong, and Wanqing Liu. "Abstract 2851: EGFR-TERT cooperation in the development of EGFR-TKI treatment induced pulmonary fibrosis." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-2851.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Reports on the topic "EGFR TKI"

1

Song, Yaowen, Shuiyu Lin, Jun Chen, Silu Ding, and Jun Dang. First-line treatment with TKI plus brain radiotherapy vs TKI alone in EGFR-mutated non-small-cell lung cancer with brain metastases: a systematic review and meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, January 2023. http://dx.doi.org/10.37766/inplasy2023.1.0013.

Full text
Abstract:
Review question / Objective: It remains uncertain whether first-line treatment with upfront brain radiotherapy (RT) in combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) is superior to EGFR-TKIs alone in EGFR-mutated non-small-cell lung cancer with newly diagnosed brain metastases (BMs). We performed a meta-analysis to address this issue. Condition being studied: Brain radiotherapy (RT) has been shown to damage the blood-brain barrier (BBB) and improve the concentration of EGFR-TKIs in the CSF. Additionally, RT can result in a reduction of EGFR-TKIs resistance. Therefore, EGFR-TKIs in combination with brain RT should be more effective than EGFR-TKIs alone theoretically. However, results from retrospective studies are inconsistent. There is the possibility that patients characteristics or brain RT technique affect the efficacy of treatments. To date, there is still no randomized controlled trials (RCTs) comparing the two treatment strategies.
APA, Harvard, Vancouver, ISO, and other styles
2

Wang, Zexian, Yaru Guo, Xiaojin Wu, Xiaohan Qin, Zhiling Wan, and Chen Liu. Bevacizumab plus Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor versus EGFR-TKI alone for advanced EGFR-mutant non-small cell lung cancer: a meta-analysis of randomized clinical trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, December 2023. http://dx.doi.org/10.37766/inplasy2023.12.0059.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Qin, Xiaohan, Yaru Guo, Xiaojin Wu, Zexian Wang, Zhiling Wan, and Chen Liu. Chemotherapy plus Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor versus EGFR-TKI alone for advanced EGFR-mutant non-small cell lung cancer: a meta-analysis of randomized clinical trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, January 2024. http://dx.doi.org/10.37766/inplasy2024.1.0128.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Lu, Yan, Chenbing Sun, Yu Liu, Ji Xu, Hongyong Deng, Lijing Jiao, Yabin Gong, and Ling Xu. Chinese Herbal Medicine Combined with EGFR-TKI in Advanced Non-small Cell Lung Cancer with EGFR Sensitive Mutation: a systematic review and meta-analysis protocol. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, November 2020. http://dx.doi.org/10.37766/inplasy2020.11.0063.

Full text
APA, Harvard, Vancouver, ISO, and other styles
5

wan, zhiling, yaru Guo, xiaojin Wu, zexian Wang, xiaohan Qin, and Chen Liu. Efficacy of immunotherapy combined with chemotherapy in NSCLC patients with EGFR-TKI resistance: a meta-analysis of randomized clinical trials. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, February 2024. http://dx.doi.org/10.37766/inplasy2024.2.0075.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Lin, Chutong, Fengling Hu, Hongling Chu, Peng Ren, Shanwu Ma, Jingdi Wang, Jie Bai, Xuan Han, and Shaohua Ma. The Role of EGFR-TKIs as Adjuvant Therapy in EGFR Mutation-Positive Early-Stage NSCLC: a meta-analysis. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, October 2020. http://dx.doi.org/10.37766/inplasy2020.10.0098.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Zhang, yao. Traditional Chinese medicine combined with EGFR-TKIs in the treatment of advanced non-small cell lung cancer with classical EGFR mutations. INPLASY - International Platform of Registered Systematic Review and Meta-analysis Protocols, February 2023. http://dx.doi.org/10.37766/inplasy2023.2.0042.

Full text
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'EGFR TKI' for particular source types:
Journal articles Dissertations / Theses
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography