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HGF/MET and MSP/RON are two closely related signaling pathways that support the growth and survival of cancer cells, promote their metastatic spread and interfere with the response of cancer cells to therapy. MET and RON kinase activation is triggered through binding by their respective ligands, HGF and MSP. Overexpression, amplification, or mutational activation of the receptors lead to ligand‐independent signaling. Due to their role in tumor progression and therapeutic resistance, the HGF/MET and MSP/RON pathways have emerged as valid clinical therapeutic targets in a variety of cancers. MET and RON are often co‐expressed in cancer. They can form heterodimers, and can trans‐phosphorylate each other. Because of the extensive cross‐talk between MET and RON, dual inhibitors of MET and RON signaling may be more effective than treatment with individual inhibitors alone.

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