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Cancer Treat Rev. 2018 May;66:95-103. doi: 10.1016/j.ctrv.2018.04.008. Epub 2018 Apr 26.

Untying the gordion knot of targeting MET in cancer.

Author information

1
Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
2
Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
3
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
4
Department of Bioinformatics & Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
5
Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
6
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States. Electronic address: dshong@mdanderson.org.

Abstract

Despite compelling evidence backing the crucial role of a dysregulated MET axis in cancer and a myriad of agents targeting this pathway in active clinical development, the therapeutic value of MET inhibition in cancer oncology remains to be established. Although a series of disappointing clinical trials, at first, lessened fervor for targeting this pathway, investigations continue unabated with a number of novel active compounds entering clinical trials. Suboptimal designs which lacked biomarker selection have been the main reason for these early failures and this has stimulated a more biomarker enriched approach lately. Fresh insights into the mechanics of diverse MET aberrations (amplifications and mutations) have allowed trial enrichment for appropriate patients in appropriate disease settings. Development of MET inhibition as a therapeutic strategy in cancer has been a lesson in itself reflecting the challenging opportunities enclosed in the genetic landscape of cancer. Here, we will review the status of MET targeted therapy in development as it stands today, discuss emerging paradigms in MET inhibition and theorize on concepts for future development. We venture to propose that in spite of early disappointments, the future of this therapeutic strategy is promising with use of appropriate predictive biomarker in the right clinical context.

KEYWORDS:

Amplification; Cancer; MET; Mutation; Targeted therapy

PMID:
29730462
DOI:
10.1016/j.ctrv.2018.04.008
[Indexed for MEDLINE]

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