MET-Targeting Anticancer Drugs-De Novo Design and Identification by Drug Repurposing
The Met protein is a cell surface receptor tyrosine kinase predominantly expressed in epithelial cells. Aberrant regulation of <i>MET</i> is manifested by numerous mechanisms including amplification, mutations, deletion, fusion of the <i>MET</i> proto-oncogene, and protein ov...
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| Main Authors: | , , |
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| Format: | Book |
| Published: |
MDPI AG,
2023-07-01T00:00:00Z.
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| Summary: | The Met protein is a cell surface receptor tyrosine kinase predominantly expressed in epithelial cells. Aberrant regulation of <i>MET</i> is manifested by numerous mechanisms including amplification, mutations, deletion, fusion of the <i>MET</i> proto-oncogene, and protein overexpression. They represent the common causes of drug resistance to conventional and targeted chemotherapy in numerous cancer types. There is also accumulating evidence that MET/HGF signaling drives an immunosuppressive tumor microenvironment and dampens the efficacy of cancer immunotherapy. Substantial research effort has been invested in designing Met-targeting drugs with different mechanisms of action. In this review, we summarized the current preclinical and clinical research about the development of Met-targeting drugs for cancer therapeutics. Early attempts to evaluate Met-targeted therapies in clinical trials without selecting the appropriate patient population did not produce satisfactory outcomes. In the era of personalized medicine, cancer patients harboring <i>MET</i> exon 14 alterations or <i>MET</i> amplification have been found to respond well to Met-inhibitor therapy. The application of Met inhibitors to overcome drug resistance in cancer patients is discussed in this paper. Given that kinases play critical roles in cancer development, numerous kinase-mediated signaling pathways are attractive targets for cancer therapy. Existing kinase inhibitors have also been repurposed to new kinase targets or new indications in cancer. On the other hand, non-oncology drugs have also been repurposed for treating cancer through kinase inhibition as one of their reported anticancer mechanisms. |
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| Item Description: | 10.3390/ddc2030031 2813-2998 |