Targeting MET Dysregulation in Cancer

Aberrant MET signaling can drive tumorigenesis in several cancer types through a variety of molecular mechanisms including gene amplification, mutation, rearrangement, and overexpression. Improvements in biomarker discovery and testing have more recently enabled the selection of patients with MET-de...

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Published inCancer discovery Vol. 10; no. 7; pp. 922 - 934
Main Authors Recondo, Gonzalo, Che, Jianwei, Jänne, Pasi A, Awad, Mark M
Format Journal Article
LanguageEnglish
Published United States 01.07.2020
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Summary:Aberrant MET signaling can drive tumorigenesis in several cancer types through a variety of molecular mechanisms including gene amplification, mutation, rearrangement, and overexpression. Improvements in biomarker discovery and testing have more recently enabled the selection of patients with MET-dependent cancers for treatment with potent, specific, and novel MET-targeting therapies. We review the known oncologic processes that activate MET, discuss therapeutic strategies for MET-dependent malignancies, and highlight emerging challenges in acquired drug resistance in these cancers. SIGNIFICANCE: Increasing evidence supports the use of MET-targeting therapies in biomarker-selected cancers that harbor molecular alterations in MET. Diverse mechanisms of resistance to MET inhibitors will require the development of novel strategies to delay and overcome drug resistance.
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ISSN:2159-8274
2159-8290
DOI:10.1158/2159-8290.cd-19-1446