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Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
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Published on: December 11, 2017

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MET/HGF pathway activation as a paradigm of resistance to targeted therapies

Brian Ko1, Tianfang He1, Shirish Gadgeel2

  • 1Department of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY 10467, USA.

Annals of Translational Medicine
|February 7, 2017
PubMed

Insights

Resistance to cancer therapies like EGFR and ALK inhibitors can occur through MET kinase activation. New trials with improved patient selection and biomarkers offer hope for effective MET-targeted cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Targeted therapies for cancers with specific genetic alterations (e.g., EGFR, ALK in non-small cell lung cancer) face significant challenges due to acquired resistance.
  • MET kinase activation is a validated bypass resistance mechanism across various cancer types, impacting treatment efficacy.
  • Understanding MET's role in bypass pathways and epithelial-mesenchymal transitions is crucial for developing effective therapeutic strategies.

Purpose of the Study:

  • To review the role of MET kinase activation as a resistance mechanism to targeted cancer therapies.
  • To discuss the development and availability of diagnostic platforms for MET-targeted therapy selection.
  • To highlight the potential of ongoing and future clinical trials incorporating advanced patient selection and predictive biomarkers for MET inhibitors.

Main Methods:

  • Literature review of studies investigating resistance mechanisms in targeted cancer therapy.
  • Analysis of biochemical pathways involving MET kinase activation in cancer.
  • Examination of current and emerging diagnostic and therapeutic strategies for MET-targeted oncology.

Main Results:

  • MET kinase activation represents a common and significant bypass resistance mechanism in cancers treated with targeted agents.
  • Diagnostic tools for identifying patients eligible for MET inhibition are increasingly available.
  • Recent clinical trials show promise due to refined patient selection and biomarker strategies.

Conclusions:

  • MET-targeted therapies hold potential for overcoming resistance in molecularly selected cancer patients.
  • Improved patient stratification and biomarker development are critical for the success of MET-targeted cancer treatments.
  • Ongoing clinical investigations are paving the way for the validation of MET-targeting as a clinically relevant strategy in oncology.
Keywords:
EGFRMETlung cancerresistancetargeted therapeuticstyrosine kinase

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