Non-small-cell lung cancer: how to manage MET exon 14 skipping mutant disease

Abstract

Several oncogenic mechanisms have been identified for MET, including MET amplification, fusions, mutations in the tyrosine kinase domain and exon 14 skipping alterations. MET exon 14 mutations are found in about 3-5% of non-small-cell lung cancers. Dysregulation of the MET receptor leads to cell proliferation and survival by activation of the PI3K-AKT-TOR and RAS-RAF-MET-ERK canonical pathways. Targeting the MET tyrosine kinase domain in the setting of MET exon 14 mutations using effective MET tyrosine kinase inhibitors is a current targeted therapy option for patients with metastatic lung cancer. In this Review, we focus on the management of patients with MET exon 14 skipping alterations by addressing the biology of the MET receptor and exon 14 skipping mutations, current treatment strategies, and sequential treatment options based on resistance mechanisms to MET inhibitors in patients with non-small-cell lung cancer.

From targeted therapy to a novel way: Immunogenic cell death in lung cancer

“…HGF is a common ligand of MET, upon their binding, MET will be dimerized and auto-phosphorylate, thus leading to the activation of activity of intracellular tyrosine kinase. Activation of MET could lead to the modulation of multiple downstream signaling pathways including RAS/RAF/ERK/MAPKA, PI3K/AKT/mTOR, Wnt/βcatenin, STAT and so on, which play vital roles in regulating tumor growth, progression and migration (97). Aberrant activation of MET signaling pathway may contribute to the tumorigenesis process of lung cancer.…”