EGFR mutation

EBV-GC is characterized by distinct clinicopathological and molecular features. Pathological examination, immunophenotyping, and NGS provide significant value for diagnosis and therapeutic direction.

PIK3CA mutant-mediated cachexia can be overcome by osimertinib (Osi) treatment in Osi-sensitive GEMM. PIK3CA mutant-driven cachexia is mediated through NF-κB activation and can be dampened by combined aspirin treatment. This work provides insights into PIK3CA mutant biological function and mechanisms behind its clinical impacts, and proposes a potential strategy for clinical management.

EGFRi rechallenge is associated with significantly longer PFS, numerically longer OS, and clinically meaningful ORR as compared with non-EGFRi systemic therapy in mCRC, particularly for ctDNA RAS/RAF wild-type mCRC.

We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.

This study underscores the clinical importance of the rare germline EGFR T790M mutation in lung cancer. Detecting carriers with a family history may allow earlier diagnosis and inform targeted prevention, supporting more precise screening for high-risk individuals.

Importantly, both markers were significantly elevated in gefitinib-resistant, EGFR-mutant NSCLC cells...Given their dual roles in diagnosis and resistance, SPON1 and SPON2 are intriguing ultrasound-responsive biomarkers in EGFR-mutant NSCLC. These findings provide the groundwork for future incorporation of ultrasound-mediated delivery methods or sonodynamic treatments targeting SPON1/SPON2, opening up new possibilities for overcoming EGFR-TKI resistance and improving therapeutic effectiveness in resistant NSCLC.

Notably, HHLA2/KIR3DL3 inhibition synergized with EGFR tyrosine kinase inhibitors to enhance anti-tumor immunity and suppress tumor progression. Together, these findings identify HHLA2-KIR3DL3 as a key immunosuppressive pathway in EGFR-mutant NSCLC and may provide a rationale for therapeutic targeting to improve clinical outcomes.

We also discuss other novel therapeutic approaches to overcome EGFR-TKIs resistance, including protein degradation-targeting chimeras, poly (ADP-ribose) polymerase inhibitors, aurora kinase inhibitors, and metabolic reprogramming strategies. Finally, we summarize the main challenges associated with ADCs-based therapies and highlight future directions for optimizing treatment in EGFR-TKI-resistant NSCLC.

Furthermore, we validated the specificity of our approach by successfully detecting various mutations, including KRAS G12C, KRAS G12D, EGFR T790M and TP53 R273H, in simulated clinical samples. These findings highlight a reliable method for precise ctDNA detection, offering high specificity, selectivity, and accuracy, thus paving the way for potential cancer diagnostic application.

A growing body of evidence indicates that BAF complex mutations have important prognostic implications. These may be leveraged for risk stratification and therapeutic selection in patients with non-small cell lung cancer.

In colon and lung tumor models, NanoTACs suppressed tumor growth by 88.3%, achieved 95% degradation of wild-type and 80% of mutant EGFR, and induced extensive apoptosis without systemic toxicity. These findings established NanoTACs as a promising EGFR-targeted platform to overcome drug resistance to mAbs and TKIs by enabling effective degradation of wild-type and mutant EGFR in heterogeneous cancers.