The Role of cMet in Non-Small Cell Lung Cancer Resistant to EGFRInhibitors: Did We Really Find the Target?

Title:The Role of cMet in Non-Small Cell Lung Cancer Resistant to EGFRInhibitors: Did We Really Find the Target?

Volume: 15 Issue: 14

Author(s): Francesco Passiglia, Nele Van Der Steen, Luis Raez, Patrick Pauwels, Ignacio Gil-Bazo, Edgardo Santos, Daniele Santini, Giovanni Tesoriere, Antonio Russo, Giuseppe Bronte, Karen Zwaenepoel, Federico Cappuzzo and Christian Rolfo

Affiliation:

Keywords: cMET, cMET-Inhibitors, EGFR-TKIs resistance, HGF, NSCLC, targeted therapies.

Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal–epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpression of the HGF, have been reported in a substantial subgroup of NSCLC patients resistant to EGFR-TKIs. Several cMET-inhibitors have been developed as potential therapeutic candidates, and are currently under investigation in clinical trials. These compounds include both monoclonal antibodies and TKIs, and most of them have been investigated as dual combinations including an anti-EGFR TKI, to improve the efficacy of the available treatments, and ultimately overcome acquired resistance to EGFR-inhibitors.

Cite this article as:

Passiglia Francesco, Steen Van Der Nele, Raez Luis, Pauwels Patrick, Gil-Bazo Ignacio, Santos Edgardo, Santini Daniele, Tesoriere Giovanni, Russo Antonio, Bronte Giuseppe, Zwaenepoel Karen, Cappuzzo Federico and Rolfo Christian, The Role of cMet in Non-Small Cell Lung Cancer Resistant to EGFRInhibitors: Did We Really Find the Target?, Current Drug Targets 2014; 15 (14) . https://dx.doi.org/10.2174/138945011514141216092739