MET mutation

Case 1 received osimertinib combined with savolitinib, had 33 months of follow-up, and achieved a partial response. Case 2 received furmonertinib and achieved a complete response. NTRK2 fusion coexisting with EGFR mutations is a rare molecular characteristic of non-small cell lung cancer, accompanied by positive PD-L1 expression, and may serve as a promising biomarker for targeted therapy.

Notably, this function is absent from the closely related MST1R/RON RTK, suggesting it is a unique feature of the MET receptor. Together, these findings uncover a previously unrecognized layer of MET regulation with potential implications for the development of selective therapies targeting MET-driven cancers.

We further integrated cancer patient-derived organoid (PDO) data on drug sensitivity into the QSP framework and explored the translational utility of this hybrid drug analysis paradigm towards the design of optimal personalized treatment regimens for 5 NSCLC patients harboring MET amplification. To our knowledge, our work is the first multiscale QSP investigation of MET dysregulation for translational cancer drug research, and by integrating QSP model analyses with PDO data it has opened up a new route to facilitate future cancer personalized medicine.

Precision therapy for PSC, particularly immunotherapy-based combination strategies, has demonstrated transformative potential. However, further efforts in this field should involve clarifying the relevant EMT and tumor heterogeneity mechanisms, optimizing existing treatment regimens, and conducting targeted clinical trials, as these measures may advance individualized precision therapy for patients with PSC and improve their outcomes.

A plasma sample serves as a supplement for identifying GPS when a tissue sample is unavailable. Moreover, the integration of FISH, NGS, and ddPCR provided a comprehensive assessment of MET amplification.

Primary and acquired MET mutations in NSCLC exhibit distinct genomic characteristics. Patients harboring concurrent EGFR mutations in NSCLC may derive less benefit from MET-TKI and ICI, whereas those harboring TP53 co-mutations tend to experience more favorable outcomes compared with TP53 wild-type NSCLC patients when treated with MET-TKI.

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.

Savolitinib plus osimertinib demonstrated numerically higher clinical activity versus savolitinib plus placebo in all patients and patients with higher MET biomarker cutoffs.

P2, N=100, Active, not recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial primary completion date: Sep 2025 --> Apr 2028

The present study marks the initial discovery of MET exon 14 skipping and EGFR Del19 in a single patient, who achieved partial response through a treatment plan involving Osimertinib and Gumarontinib. These findings provide valuable perspectives on treatment approaches for individuals sharing similar genetic profiles.

These cells exhibited markedly enhanced cytotoxicity against tumour cells overexpressing c-Met, accompanied by increased release of key effector cytokines such as interferon-γ. This research framework offers a precise, synergistic therapeutic strategy to overcome limitations in CAR-T therapy response within serous ovarian carcinoma.

P1/2, N=862, Recruiting, DualityBio Inc. | Trial completion date: Jan 2028 --> May 2028 | Trial primary completion date: Sep 2027 --> Dec 2027