Open AccessSafety and Tolerability of c-MET Inhibitors in Cancer
Author(s) -
Alberto Puccini,
Nagore I. Marín-Ramos,
Francesca Bergamo,
Marta Schirripa,
Sara Lonardi,
HeinzJosef Lenz,
Fotios Loupakis,
Francesca Battaglin
Publication year - 2019
Publication title -
drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.377
H-Index - 124
eISSN - 1179-1942
pISSN - 0114-5916
DOI - 10.1007/s40264-018-0780-x
Subject(s) - medicine , cabozantinib , c met , tolerability , crizotinib , clinical trial , tyrosine kinase , hepatocyte growth factor , cancer , pharmacology , cancer research , oncology , adverse effect , receptor , lung cancer , malignant pleural effusion
The role of aberrant hepatocyte growth factor receptor (c-MET, also known as tyrosine-protein kinase MET)/hepatocyte growth factor (HGF) signaling in cancer progression and invasion has been extensively studied. c-MET inhibitors have shown promising pre-clinical and early phase clinical trial anti-tumor activity in several tumor types, although results of most phase III trials with these agents have been negative. To date, two small molecule c-MET inhibitors, cabozantinib and crizotinib, have been approved by regulatory authorities for the treatment of selected cancer types, but several novel c-MET inhibitors (either monoclonal antibodies or small molecule c-MET tyrosine kinase inhibitors) and treatment combinations are currently under study in different settings. Here we provide an overview of the mechanism of action and rationale of c-MET inhibition in cancer, the efficacy of approved agents, and novel promising c-MET-inhibitors and novel targeted combination strategies under development in different cancer types, with a focus on the safety profile and tolerability of these compounds.