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Targeting MET Dysregulation in Cancer

Gonzalo Recondo1, Jianwei Che2,3, Pasi A Jänne4,5

  • 1Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.

Cancer Discovery
|June 14, 2020
PubMed

Insights

Aberrant MET signaling drives cancer via genetic alterations. MET-targeting therapies show promise in biomarker-selected patients, but acquired drug resistance presents challenges.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Genetics

Background:

  • Aberrant MET signaling, driven by MET gene amplification, mutation, rearrangement, or overexpression, is implicated in tumorigenesis across various cancer types.
  • Advances in biomarker discovery and testing facilitate patient selection for MET-targeted therapies in MET-dependent cancers.

Purpose of the Study:

  • To review oncologic processes activating MET.
  • To discuss therapeutic strategies for MET-dependent malignancies.
  • To highlight challenges in acquired drug resistance to MET inhibitors.

Main Methods:

  • Literature review of oncologic processes activating MET.
  • Analysis of current therapeutic strategies for MET-dependent cancers.
  • Examination of emerging challenges in acquired drug resistance.

Main Results:

  • MET signaling alterations are key drivers of tumorigenesis in multiple cancers.
  • Biomarker-guided selection enables effective use of novel MET-targeting therapies.
  • Acquired drug resistance is an emerging challenge requiring new therapeutic strategies.

Conclusions:

  • Growing evidence supports MET-targeting therapies in biomarker-selected cancers with MET alterations.
  • Diverse resistance mechanisms necessitate the development of novel strategies to overcome drug resistance and improve patient outcomes.

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