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Safety and Tolerability of c-MET Inhibitors in Cancer

Author

Listed:
  • Alberto Puccini

    (University of Southern California
    IRCCS Ospedale Policlinico San Martino)

  • 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
    Veneto Institute of Oncology IOV-IRCCS)

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.

Suggested Citation

  • Alberto Puccini & Nagore I. Marín-Ramos & Francesca Bergamo & Marta Schirripa & Sara Lonardi & Heinz-Josef Lenz & Fotios Loupakis & Francesca Battaglin, 2019. "Safety and Tolerability of c-MET Inhibitors in Cancer," Drug Safety, Springer, vol. 42(2), pages 211-233, February.
    • Handle: RePEc:spr:drugsa:v:42:y:2019:i:2:d:10.1007_s40264-018-0780-x
    DOI: 10.1007/s40264-018-0780-x
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    Cited by:

    1. Rashmi R. Shah & Giuseppe Curigliano, 2019. "Safety of Novel Targeted Therapies in Oncology," Drug Safety, Springer, vol. 42(2), pages 157-158, February.

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