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Liver cancer

Fibroblast growth factor 19 (FGF19); fibroblast growth factor receptor 4 (FGFR4; CD334)

Mouse studies suggest an FGF19 variant that activates a subset of pathways downstream of FGFR4 could help treat liver cancer. In mice, adeno-associated viral (AAV) vector-induced expression of FGF19 variants showed that the M70 variant bound Fgfr4 but did not induce tumor formation or activation of a tumor-associated signaling pathway in liver cells. In mice, coexpression of FGF19 and the M70 variant resulted in decreased tumor formation compared with expression of FGF19 alone, indicating that M70 can counter the known tumor-promoting activity of wild-type FGF19. Next steps include evaluating M70 for clinical use in primary biliary cirrhosis, hepatocellular carcinoma and nonalcoholic steatohepatitis.
Isis Pharmaceuticals Inc. has ISIS-FGF4Rx, an antisense oligonucleotide targeting FGFR4 mRNA, in Phase I testing to treat obesity.
Blueprint Medicines has BLU9931, a small molecule inhibitor of FGFR4, in preclinical development to treat liver cancer.

SciBX 7(19); doi:10.1038/scibx.2014.556
Published online May 15, 2014

Patent applications filed; available for licensing from NGM Biopharmaceuticals Inc.

Zhou, M. et al. Cancer Res.; published online April 11, 2014;
Contact: Lei Ling, NGM Biopharmaceuticals Inc., South San Francisco, Calif.