MET (MET proto-oncogene, receptor tyrosine kinase)

The Pan Lung Cancer PCR Panel was highly concordant with other assays. The panel can be performed in local laboratories with a rapid turnaround time and represents an attractive alternative to next-generation sequencing for patients with lung cancer.

Savolitinib demonstrated robust and durable efficacy in patients with METex14-mutated, locally advanced NSCLC with manageable safety, supporting savolitinib as a treatment option in this disease setting. HUTCHMED, AstraZeneca.

The incremental cost-effectiveness ratio (ICER) of Capmatinib treatment vs. Tepotinib treatment was calculated at 60,977.28 USD/QALY. Tepotinib was not cost-effective compared to Capmatinib as the second-line treatment for advanced or metastatic NSCLC patients with MET exon 14 skipping mutations in China.

P2/3, N=854, Recruiting, AbbVie | Trial completion date: Nov 2036 --> Dec 2031 | Trial primary completion date: Nov 2036 --> Dec 2031

P1, N=55, Recruiting, DeuterOncology | N=25 --> 55 | Trial completion date: Dec 2026 --> Sep 2028 | Trial primary completion date: Dec 2025 --> Sep 2027 | Active, not recruiting --> Recruiting

Early clinical candidates, such as EZN-3042 and ALN-VSP, achieved target engagement and biological activity, while limitations included variable tumour uptake, dose-limiting toxicities, and complex pharmacokinetic behaviour. Translation to clinical practice will depend on optimised delivery platforms, reproducible pharmacokinetic/pharmacodynamic synchronisation, and rigorous evaluation of safety and off-target effects. Overall, current evidence highlights substantial potential for siRNA-drug co-delivery while emphasizing key challenges to overcome in achieving durable clinically meaningful outcomes.

Inhibition of downstream signaling and cell proliferation by vabametkib plus lazertinib were evaluated in osimertinib-resistance NSCLC cell lines (HCC827-AR) and patient-derived organoid (YUO-010) by western blot and Cell Titer-Glo assay. Consistent with the in vitro findings, treatment with vabametkib plus lazertinib produced pronounced suppression of tumor growth in both models through a synergistic mechanism. These findings establish vabametkib plus lazertinib as a promising strategy for MET-amplified NSCLC, currently under evaluation in an ongoing phase II clinical trial (NCT05541822).

Silencing of SNHG10 decreases cell survival, proliferation, clonogenicity, EMT tumor growth through the EGFR/AKT/ERK/mTOR axis, and restores the expression of miR-150-5p, which eventually downregulates VEGF-A. SNHG10 downregulation enhanced the gemcitabine sensitivity in gemcitabine-resistant PDAC cells.

Collectively, c-MET is a core target in oncology, with rapidly evolving therapeutic agents and strategies. The development of innovative drugs and rational combinations will continue to refine c-MET-targeted therapy and expand treatment options for patients with c-MET-aberrant tumors.

Temab-A monotherapy demonstrated antitumor activity and a manageable safety profile in patients with advanced GEA. The findings support further clinical development of Temab-A, particularly in combination with other agents to improve outcomes for patients with 2L+ GEA.

ZM fusion was associated with a worse prognosis in both astrocytoma (OS p < 0.001, PFS p < 0.001) and glioblastoma (OS, p = 0.252; PFS, p = 0.010) patients. We highlight the utmost relevance of ZM fusion as an adverse prognostic factor in astrocytoma (11/382, 2.88%) and glioblastoma grade 4 (11/401, 2.74%) patients and suggest that the grading of these tumors should be refined.

We investigated the effects of short-term (5 days) and long-term (≥5 weeks) exposure to the IDH1 inhibitor AGI-5198 on radiation-induced cytotoxicity...Effects were comparable to short-term treatment, while radiation responses varied by genetic context. No deleterious interaction between IDHi and IR was observed in endogenous IDH-mutant cells except for MGG18 Tet+ supporting integration of IDHi with radiotherapy in IDH mutant gliomas.