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Biagio Ricciuti: Our collaborative effort to characterize MET kinase domain mutations as novel and targetable alterations in NSCLC and other cancer types
Apr 8, 2024, 14:35

Biagio Ricciuti: Our collaborative effort to characterize MET kinase domain mutations as novel and targetable alterations in NSCLC and other cancer types

Biagio Ricciuti, Medical Oncologist at Dana-Farber Cancer Institute, posted on X:

Our collaborative effort to characterize MET kinase domain mutations as novel and targetable alterations in NSCLC (Non-Small Cell Lung Cancer) and other cancer types is out in Cancer Discovery! Led by scientists Federica Pecci and Seshiru Nakazawa.

Using comprehensive genomic profiling among >600,000 patients, we identified MET TKD mutations as putative oncogenic drivers across diverse cancers, with a frequency of ~0.5%. The most frequent included substitutions at positions H1094, L1195, F1200, D1228 and Y1230.

Preclinical modeling of these alterations demonstrated their oncogenic potential and differential patterns of sensitivity to type I and II MET inhibitors. 2 patients with metastatic NSCLC harboring H1094Y and F1200I mutations had partial responses to a type I MET inhibitor.

In summary, activating MET TKD mutations occurs in multiple malignancies and may confer clinical sensitivity to currently available MET inhibitors. This study highlights the importance of performing comprehensive genomic tumor profiling to detect rare but targetable drivers.

Read further.
Source: Biagio Ricciuti/X