Safety and Tolerability of c-MET Inhibitors in Cancer

Alberto Puccini, Nagore I. Marín-Ramos, Francesca Bergamo, Marta Schirripa, Sara Lonardi, Heinz-Josef Lenz, Fotios Loupakis and Francesca Battaglin ()
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Alberto Puccini: University of Southern California
Nagore I. Marín-Ramos: University of Southern California
Francesca Bergamo: Veneto Institute of Oncology IOV-IRCCS
Marta Schirripa: Veneto Institute of Oncology IOV-IRCCS
Sara Lonardi: Veneto Institute of Oncology IOV-IRCCS
Heinz-Josef Lenz: University of Southern California
Fotios Loupakis: Veneto Institute of Oncology IOV-IRCCS
Francesca Battaglin: University of Southern California

Drug Safety, 2019, vol. 42, issue 2, No 5, 233 pages

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1007/s40264-018-0780-x

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