EGFR T790M

This study demonstrates that EGFR-targeted therapy, when used in a first-line setting, significantly improves OS and PFS in this population. Further research is warranted to optimise treatment strategies, particularly in resource-limited settings.

In participants with atypical EGFR-mutated advanced NSCLC, amivantamab-lazertinib demonstrated clinically meaningful antitumor activity with no new safety signals.

Our results further reveal that the MUC1-C-driven STAT1 inflammatory response promotes resistance of patient-derived (i) EGFR mutant NSCLC cells with MET amplification to the combination of osimertinib+MET TKIs, and (ii) EGFR(T790M/C797S) NSCLC cells to the 4th generation EGFR TKI TQB3804. Of clinical significance, we report that NSCLC cells dependent on MUC1-C for TKI resistance are druggable with an antibody-drug conjugate (M1C ADC) in vitro and in a PDX tumor model. These findings demonstrate that MUC1-C (i) is essential for TKI resistance of NSCLC cells by driving an inflammatory memory response and (ii) is a target for M1C ADC treatment of TKI-refractory NSCLCs.

Kaplan-Meier and Cox regression analyses revealed no significant survival difference between hereditary and somatic mutation groups (median OS 24.9 vs. 24.0 months; log-rank p = 0.69; HR = 1.19; 95% CI, 0.52-2.73). These findings indicate that germline EGFR T790M represents a measurable hereditary variant within the South Caucasus population and emphasize the need to integrate germline testing into diagnostic workflows and familial risk assessment strategies for EGFR-driven NSCLC.

Patients received RAM (10 mg/kg every 2 wk) plus GEF (250 mg once daily) until disease progression (period 1); patients with disease progression who acquired a T790M mutation received RAM plus osimertinib (80 mg once daily) (period 2). Treatment-emergent T790M rate post progression was 81.3%. RELAY+ revealed a favorable benefit-risk profile for RAM plus GEF in East Asian patients with untreated EGFR-mutated metastatic NSCLC, supporting RAM plus GEF as an alternative first-line treatment option, particularly in those with an L858R mutation.

The study identified multiple genomic characteristics associated with primary and secondary resistance to first-line afatinib treatment in EGFR- and ERBB2-positive subpopulations.

Autophagy inhibition by 3-methyladenine and ATG gene silencing effectively decreased the cytotoxic effect of GMI, suggesting that GMI induces autophagic cell death in H1975/TR cells. This study is the first to reveal the novel role of GMI in inducing cytotoxic effects in H1975 cells and H1975/TR cells with osimertinib resistance through two different forms of cell death: apoptosis and autophagy, respectively.

Two patients experienced disease recurrence and were successfully switched to osimertinib upon identification of an EGFR (T790M) mutation. This study suggests a potential DFS benefit and well-tolerated profile of adjuvant icotinib in patients with EGFR-mutated high-risk stage IB NSCLC. However, longer-term follow-up is necessary to assess the long-term outcomes.

It effectively inhibited colony formation, migration of H1975™ cells, induced G0/G1 arrest, and promoted apoptosis through suppressing EGFR and AKT phosphorylation. These findings demonstrate the potential of optimizing the dibenzodiazepinone framework for developing novel potent molecules against osimertinib resistant NSCLC cells, providing valuable insights for future research.

Radiogenomics is best viewed as a complement to biopsy rather than a replacement. Real-world impact now depends on harmonized protocols, leakage-free external validation, explainable and uncertainty-aware models, and integration with multi-omics decision support to deliver reliable, patient-centered lung cancer care.

Plasma ctDNA assessment facilitates the evaluation of treatment efficacy, monitoring disease progression, and informing second-line treatment options. ClinicalTrials.gov NCT04425187.