Journal
JOURNAL OF BIOCHEMISTRY
Volume 157, Issue 5, Pages 271-284Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jb/mvv027
Keywords
drug resistance; growth factor; molecular targeted drugs; receptor tyrosine kinase; regenerative medicine
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Funding
- Ministry of Education, Culture, Science, Sports, and Technology of Japan [23790221, 26460145, 20390077, 24300329]
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Grants-in-Aid for Scientific Research [26460145, 20390077, 15K14473, 23790221] Funding Source: KAKEN
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Activation of the hepatocyte growth factor (HGF)-Met pathway evokes dynamic biological responses that support the morphogenesis, regeneration and survival of cells and tissues. A characterization of conditional Met knockout mice indicates that the HGF-Met pathway plays important roles in the regeneration, protection and homeostasis of cells such as hepatocytes, renal tubular cells and neurons. Preclinical studies in disease models have indicated that recombinant HGF protein and expression plasmid for HGF are biological drug candidates for the treatment of patients with diseases or injuries that involve impaired tissue function. The phase-I and phase-I/II clinical trials of the intrathecal administration of HGF protein for the treatment of patients with amyotrophic lateral sclerosis and spinal cord injury, respectively, are ongoing. Biological actions of HGF that promote the dynamic movement, morphogenesis and survival of cells also closely participate in invasion-metastasis and resistance to the molecular-targeted drugs in tumour cells. Different types of HGF-Met pathway inhibitors are now in clinical trials for treatment of malignant tumours. Basic research on HGF and Met has lead to drug discoveries in regenerative medicine and tumour biology.
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