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, Francesca Battaglin

Research output: Contribution to journalReview article

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.

Original languageEnglish
Pages (from-to)211-233
Number of pages23
JournalDrug Safety
Volume42
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Anilides/adverse effects
  • Animals
  • Antineoplastic Agents/adverse effects
  • Chemical and Drug Induced Liver Injury/diagnosis
  • Clinical Trials as Topic/methods
  • Humans
  • Protein Kinase Inhibitors/adverse effects
  • Proto-Oncogene Proteins c-met/antagonists & inhibitors
  • Pyridines/adverse effects
  • Receptor Protein-Tyrosine Kinases/antagonists & inhibitors

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