Gene expression in NSCLC cancer cell with EGFR-TKI resistance after statin treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE268267 | GEO | 2025/05/23
REPOSITORIES: GEO
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Project description:Gene expression in NSCLC cancer cell with EGFR-TKI resistance after statin treatment
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Project description:The epidermal growth factor receptor (EGFR) is a kind of receptor tyrosine kinase (RTK) that plays a critical role in the initiation and development of malignant tumors via modulating downstream signaling pathways. In non-small cell lung cancer (NSCLC), the activating mutations located in the tyrosine kinase domains of EGFR have been demonstrated in multiple researches as the "Achilles' heel" of this deadly disease since they could be well-targeted by epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). However, it's still too early to celebrate since the first-generation EGFR-TKIs such as gefitinib and erlotinib have only achieved limited clinical benefits and acquired resistance to this kind of drugs occurred inevitably in almost all the NSCLC patients. In order to make the most of EGFR-TKIs and develop more effective regimens for the NSCLC patients, researchers majoring in different aspects start a battle against EGFR-TKI resistance. Challenging as it is, we still progress stably and step firmly toward the final victory. This review will summarize the major mechanisms of acquired resistance to EGFR-TKIs, and then discuss the development of rationally designed molecular target drugs in accordance with each mechanism, in the hope of shedding light on the great achievements we have obtained and tough obstacles we have to overcome in the battle against this deadly disease.
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Project description:The experiment is part of a study using systems biology approach to analyze muscle gene expression and UPLC-MS based plasma lipidomics profiling data to illuminate relevant biological pathways and to find potential biomarker candidates related to statin-induced changes in muscle metabolism.
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Project description:Third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for patients harboring T790M after first-generation EGFR-TKI resistance. However, the impact of acquired EGFR amplification on the efficacy of third-generation EGFR-TKI against T790M remains uncertain. We aimed to investigate whether the presence of acquired EGFR amplification after first-generation EGFR-TKI resistance influences the efficacy of third-generation EGFR-TKI in patients with advanced non-small-cell lung cancer (NSCLC). We reviewed data from 275 advanced NSCLC patients harboring T790M after first-generation EGFR-TKI resistance. Patients were categorized into two groups based on the presence or absence of acquired EGFR amplification identified through next-generation sequencing (NGS) after first-line EGFR-TKI treatment. We evaluated the efficacy of osimertinib used as a second-line treatment. Among these patients, 59 exhibited acquired EGFR amplification, while 216 did not. The median progression-free survival (PFS) was 12.20 months in the EGFR amplification group and 12.03 months in the non-amplification group (p = 0.011), with median overall survival (OS) of 33.90 months and 23.30 months, respectively (p = 0.164). Multivariate analysis of PFS revealed that acquired EGFR amplification and EGFR 19del were independent prognostic factors for patients with T790M undergoing osimertinib. Additionally, subgroup analysis indicated a prolonged PFS in patients with EGFR 19del compared to those with EGFR 21L858R (p = 0.034) in the EGFR amplification group. Following first-generation EGFR-TKI resistance, advanced EGFR-mutant NSCLC patients harboring both acquired T790M and EGFR amplification are likely to experience enhanced PFS with osimertinib. This phenomenon is particularly noteworthy among individuals with EGFR 19del.
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