Methods to inhibit the emergence or progression of hepatocellular carcinoma with estrogens or estrogen-like compounds

The inventors have shown that the observed pronounced male bias in hepatocellular carcinoma (HCC) is due to gender-specific differences in production of interleukin 6 by Kupfer cells. Estrogen inhibits IL-6 induction, and it has been demonstrated that estrogen-mediated inhibition of IL-6 reduces liver cancer risk in females and may be used to prevent HCC in males.

Men have been found to be more three times likely than women to develop HCC, and this gender disparity is even more pronounced in rodent models of HCC. The inventors have shown that in mice, IL-6, produced in response to chemically-induced HCC, is found in much greater amounts in male mice than in similarly treated female mice. In IL-6 knockout mice, HCC was markedly reduced in the males, but there was no change in the females. In female mice, estrogen levels have been shown to suppress IL-6 production and therefore inhibit chemically-induced liver carcinogenesis. Male mice treated with estrogen before treatment to induce HCC also showed inhibition of IL-6 promoter activity and subsequently a reduced incidence of HCC.

Commercial applications: (1) Development of a clinical test for IL-6 for patients with inflammatory disease of the liver to facilitate early detection of HCC.
(2) Development of small molecule or antibody inhibitors of IL-6 which could be used to prevent progression of liver disease to HCC.
(3) Development of estrogens and estrogen-like compounds to treat/prevent progression of liver disease to HCC.

Case No: SD2007-190
Inquiries To:  invent@ucsd.edu