EGFR T790M

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.

Nearly 7% of EGFR mutations in NSCLC patients were compound mutations, which is comparable to previous reports. The presence of multiple mutations, particularly those involving T790M , may be associated with potential resistance to first-line EGFR -TKIs. We describe a triple mutation involving del19 + G719X + S768I , which represents an uncommon scenario.

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.

P2, N=36, Active, not recruiting, Shandong Cancer Hospital and Institute

The results suggest that carmofur and B13 are promising alternatives for therapeutic targets in drug-resistant lung cancer cells.

P1/2, N=32, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2028

In a small-sample-size test, the ESEA system achieved 100% sensitivity and specificity in pleural effusion samples (n=5) and a 100% ctDNA detection rate in patients with extracranial lesions and disease progression (n=6). These results highlight its potential as a cost-effective, highly sensitive, and robust platform for dynamic, real-time companion diagnostics, as well as non-invasive monitoring of treatment response and tumor evolution.

T790M-positive samples showed clearly higher measured DNA concentration values after hybridization (5.9-7.4 ng/µL; mean = 6.7 ± 0.6 ng/µL), whereas negative and control samples remained low (1.7-2.3 ng/µL), confirming the analytical specificity and reproducibility of the developed system.This platform offers a rapid, cost-effective, and portable approach for mutation detection without requiring complex instrumentation. The CNT-Fe3O4-probe nanoplatform demonstrates promising potential for future translation into liquid biopsy applications and personalized therapeutic monitoring in NSCLC.

This study represents the latest investigation of resistance mechanisms to afatinib in NSCLC patients with nonclassical mutations. The mechanism of resistance to EGFR-TKI in this study was discovered different from that of patients with classical mutations.

P1, N=36, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Feb 2027 | Trial primary completion date: Jun 2026 --> Feb 2027

Exploiting these vulnerabilities, Unesbulin (PTC596), a tubulin-binding agent with BMI1 inhibitory activity, triggers mitotic catastrophe, mechanistically induces apoptosis in vitro and drives regression of resistant xenografts in vivo. Our findings establish BMI1 as a key mediator of Osimertinib resistance and aggressiveness, uncovering a mutation-context-dependent mitotic vulnerability that can be therapeutically exploited, providing a rationale for targeting BMI1 and mitotic abnormalities to overcome resistance in T790M/L858R backgrounds.

P1/2, N=67, Recruiting, D3 Bio (Wuxi) Co., Ltd | Active, not recruiting --> Recruiting | Trial completion date: Apr 2028 --> Aug 2028 | Trial primary completion date: Apr 2028 --> Aug 2028