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.

P1, N=5, Active, not recruiting, City of Hope Medical Center | Trial completion date: Apr 2026 --> Mar 2027 | Trial primary completion date: Apr 2026 --> Mar 2027

P3, N=204, Recruiting, Sixth Affiliated Hospital, Sun Yat-sen University | Not yet recruiting --> Recruiting

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.

P1/2, N=400, Recruiting, Bayer | Trial primary completion date: Nov 2026 --> Mar 2026

P2, N=66, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Not yet recruiting --> Recruiting

Furmonertinib shows promising intracranial efficacy with manageable safety as first-line treatment for EGFR-mutated NSCLC with CNS metastases. This study is registered at ClinicalTrials.gov (NCT05379803).

Importantly, combining cetuximab with the GDH1 activity inhibitor R162 curbed tumor metabolic adaptation, reversed TIME remodeling, and suppressed KRAS activation, thereby preventing immune escape and metastatic progression. Our findings unveil the EGFR/GDH1/αKG/ALKBH5 axis as a key modulator of cetuximab response and suggest that post-treatment monitoring of blood αKG may help identify patients who could benefit from GDH1 inhibition to augment immunotherapy and KRAS-targeted strategies.

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.

Patients with high TEPGS exhibited resistance to immunotherapy but responded to a BRAF V600E inhibitor, while TEPGS showed tentative value for predicting cetuximab response and preliminary utility for bevacizumab. Functional assays confirmed ARPC1B as an oncogene. Our findings establish TEPGS as a valuable biomarker for prognostic stratification and tailored therapy selection in CRC.

The past two decades have witnessed transformative advances in HER2-targeted therapeutics, exemplified by tyrosine kinase inhibitors (TKIs), including first-generation reversible pan-HER (e.g., lapatinib), second-generation covalent pan-HER (neratinib, pyrotinib), and novel selective HER2 inhibitors (tucatinib, sevabertinib, zongertinib). This review comprehensively summarizes recent advances in HER2-targeted TKIs and their emergent resistance mechanisms, further analyzing strategies to both mitigate off-target toxicity and overcome resistance through rational design of selective HER2 inhibitors. Collectively, these insights provide a roadmap for developing next-generation precision therapies in HER2-driven cancers.