Cancer

Patient sample and mouse studies suggest inhibiting the IL-6-JAK-STAT3 axis could help treat FGF19-driven hepatocellular cancer (HCC). In HCC patients, high tumor levels of FGF19 were associated with poor overall survival and correlated with high expression levels of the STAT3 downstream targets survivin (BIRC5), B cell lymphoma 2 (BCL-2; BCL2) and heat shock protein family A member 4 (HSPA4). In a mouse model of FGF19-driven HCC, hepatocyte-specific knockout of STAT3, systemic knockout of IL-6, an anti-IL-6 antibody or the pan-JAK inhibitor Xeljanz tofacitinib decreased tumor growth and tumor numbers compared with normal STAT3 and IL-6 expression, an isotype-matched control antibody or vehicle. Next steps by could include identifying and testing inhibitors of the IL-6-JAK-STAT3 axis in FGF19-driven HCC models.

Pfizer Inc. and Takeda Pharmaceutical Co. Ltd. market Xeljanz to treat rheumatoid arthritis. Pfizer also has the compound in registration for psoriasis, Phase III testing for juvenile idiopathic arthritis (JIA), psoriatic arthritis and inflammatory bowel disease (IBD), Phase II testing for dry eye, and Phase I testing for dermatomyositis...