MET alterations and therapeutic strategies in non-small cell lung cancer

Abstract

Mesenchymal to epithelial transition factor (MET) often plays a crucial role in cell homeostasis, motility and apoptosis, while its alterations can promote the proliferation, invasion and metastasis of tumors cells. In non-small cell lung cancer (NSCLC), MET genetic alterations include MET exon 14 skipping mutations, MET amplification, MET fusion, MET-tyrosine kinase domain and overexpression. Based on the understanding of the potential therapeutic targets of MET, the investigators propose 3 strategies of MET targeting for clinical trials: MET tyrosine kinase inhibitors (TKIs), including crizotinib, capmatinib, tepotinib, savolitinib, and cabozantinib; MET or hepatocyte growth factor (HGF) monoclonal antibodies, including emibetuzumab vedotin and ficlatuzumab; and MET or HGF antibody-drug conjugate and bispecific antibodies, including telisotuzumab and amivantamab. In this article, we review the progress of MET genetic alteration and its treatment progress, hope to provide more precise treatment for the patients with MET alterations, and provide new ideas for the efficacy and drug resistance of targeted therapy and immunotherapy.

Keywords

• non-small cell lung cancer
• molecular targeted therapy
• proto-oncogene proteins c-met