MET exon 14 mutation

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.

They were treated with savolitinib as the second-line treatment after previously receiving AP regimens (pemetrexed + cisplatin). The case series demonstrated that savolitinib has a favorable clinical efficacy and safety profile, suggesting its potential as a key therapeutic option for elderly patients with NSCLC harboring METex14 skipping mutations. The treatment offers sustained survival benefits and is well-tolerated.

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.

Utilising a robust next-generation sequencing platform, we have identified this mutation in 5.3% of cases in our cohort. In the absence of information on MET exon 14 skipping from India, this case series will throw some light on this variation in our subcontinent and highlights the fact that the real-world effectiveness of MET inhibitors like Tepotinib and Capmantinib might be lower than expected.

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.

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

SAC was an aggressive NSCLC subtype, with KRAS and METex14 as the most common driver mutations. Given the high prevalence of PD-L1 expression in SAC, further research on immunotherapy efficacy in this group is warranted.

P1/2, N=231, Recruiting, Regeneron Pharmaceuticals | Active, not recruiting --> Recruiting

Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches.