MET: A New Promising Biomarker in Non-Small-Cell Lung Carcinoma

Abstract

Non-small-cell lung cancer (NSCLC) leads cancer-related deaths worldwide. Mutations in the kinase domain of the EGFR gene provide sensitivity to tyrosine kinase inhibitors (TKI) drugs. TKI show initial response rates over 75% in mutant EGFR-NSCLC patients, although most of these patients acquire resistance to EGFR inhibitors after therapy. EGFR-TKI resistance mechanisms include amplification in MET and its ligand, and also MET mutations. MET signaling dysregulation has been involved in tumor cell growth, survival, migration and invasion, angiogenesis and activation of several pathways, therefore representing an attractive target for anticancer drug development. In this review, we will discuss MET-related mechanisms of EGFR-TKI resistance in NSCLC, as well as the main drugs targeted to inhibit MET pathway.

Keywords::

• EGFR
• MET
• pharmacogenetics
• resistance
• targeted therapies
• TKI

Disclosure

The results of this work are part of the doctoral thesis presented by C Pérez-Ramírez at the University of Granada.

Financial & competing interests disclosure

This work was partly supported by a contract for MCañadas-Garre (Técnicos de Apoyo Subprogram) from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad and a research grant for C Pérez-Ramírez, from Ministerio de Educación, Cultura y Deporte. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was partly supported by a contract for MCañadas-Garre (Técnicos de Apoyo Subprogram) from Instituto de Salud Carlos III, Ministerio de Economía y Competitividad and a research grant for C Pérez-Ramírez, from Ministerio de Educación, Cultura y Deporte. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.