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:
关键词:
cMET
摘要: 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.
