Tagrisso (osimertinib)

MET amplification alters the balance of EGFR/MET/ERBB3 dimerization, leading to a shift in signaling dependence from EGFR to MET. These findings provide insight into therapeutic strategies for EGFR-mutated NSCLC.

Translational studies in human NSCLC-derived PC9 cells further demonstrated that SAHA enhances osimertinib antitumor efficacy while alleviating cardiotoxicity. Collectively, these findings define HDAC-dependent epigenetic repression as a key mechanism underlying osimertinib-induced cardiotoxicity and identify HDAC inhibition as a therapeutically actionable strategy to improve both cardiac safety and cancer treatment efficacy.

In routine practice, first-line osimertinib shows robust effectiveness but lower rwOS than expected and substantial post-progression attrition. These findings underscore the need for risk-adapted treatment strategies and support prospective evaluation of OPD management approaches, including integration of LAT alongside contemporary systemic options.

This case suggests that dose reduction can weaken the effect of osimertinib on the CNS and that maintaining dose intensity using granulocyte colony-stimulating factor support is a viable and effective strategy for controlling CNS lesions in eloquent areas when local therapy is contraindicated.

Genetic ablation of TRMT1 or pharmacological targeting of USP25 with the small-molecule inhibitor AZ1 disrupted this pathway, restored ROS accumulation, and re-sensitized resistant tumors to Osimertinib in patient-derived organoids and in vivo models. Our findings reveal tRNA epitranscriptomic reprogramming as a novel mechanism of EGFR-TKI resistance and position the ATXN3/USP25/TRMT1 axis as a therapeutically actionable target to overcome Osimertinib resistance in lung cancer.

Reported PFS values were: replacement EGFR-TKI (1.9-4.4 months), platinum-pemetrexed chemotherapy (1.6-20.7 months), osimertinib plus platinum-pemetrexed (3.9-6.9 months), chemotherapy plus anti-angiogenic agents (1.8-16.8 months), and chemotherapy plus immune checkpoint inhibitors (3.8 months). Post-progression molecular testing and, where feasible, tissue re-biopsy are important to guide subsequent treatment decisions. Second-line outcomes were variable, with chemotherapy combined with anti-angiogenic agents showing numerically longer progression-free survival in a small subgroup; however, these findings are descriptive due to the small sample size and treatment heterogeneity.

p38δ is a critical marker and regulator of epithelial identity. Its dysregulation and loss are systematically linked to EMT and drug resistance in cancer. Given its complex, context-dependent prognostic value and functional significance, p38δ holds significant potential as a therapeutic target.

EGFR tyrosine kinase inhibitors (TKIs) have transformed management, with first-line osimertinib demonstrating a median progression-free survival (PFS) of 18.9 months and overall survival (OS) of 38.6 months in the FLAURA trial...Understanding these mechanisms is critical for optimizing patient outcomes and guiding personalized therapeutic approaches. This review discusses current strategies to delay or overcome resistance and highlights emerging therapeutic avenues with the potential to reshape the management of EGFR-mutant NSCLC.

This study supports the real-world effectiveness and tolerability of first-line osimertinib. Oligoprogression was associated with longer OS compared with systemic progression, and the integration of LATs in carefully selected patients with oligoprogression may be associated with prolonged osimertinib treatment duration and favorable post-progression outcomes.

Durvalumab plus etoposide-platinum demonstrated a modest treatment response in neuroendocrine-transformed EGFR-mutated NSCLC. AEs were concordant with the known safety profiles of the combination, and no new safety signals were observed.

TP53 GOF mutations define a biologically and clinically distinct subtype of EGFR-mutant NSCLC characterized by early resistance to osimertinib.