FASgen Presents Ovarian Cancer Efficacy and Toxicology Data to the American Association for Cancer Research
News Apr 21, 2008
FASgen, Inc. presented at the AACR meeting in San Diego efficacy and toxicology data on FAS31, FASgen's lead compound for ovarian cancer. FAS31 is an inhibitor of fatty acid synthase (FASi), an enzyme that is highly expressed in many human cancers. Numerous studies have shown that pharmacological FAS inhibition is cytotoxic to a variety of human xenograft models without toxicity. In preliminary toxicity studies, FAS31 showed no observable toxicity in normal tissues in the rat or mouse.
FAS31 inhibits fatty acid synthesis in SKOV3 human ovarian cancer cells in vitro (IC-50 = 6.09 +/- 0.4 ug/ml) at a concentration similar to induce cytotoxicity (LC-50 = 5.2 +/- 2.0 ug/ml). FAS 31 (50 mg/kg/day) for 2 weeks substantially inhibited SKOV3 xenograft growth by >90% compared to vehicle. FAS activity in the treated tumor xenografts was reduced by 82%. This is consistent with published in vitro studies where inhibition of FAS pathway activity by at least 20% led to brisk apoptosis in human cancer cells. No gross or microscopic organ toxicity was identified.
In maximally tolerated dose studies, male and female rats were challenged with increasing single doses of FAS 31 ranging from 0 (vehicle) to 1000 mg/Kg ip or po and followed for 8 days. Aside from one death in the female rats treated with 1000 mg/Kg (ip), no overt toxicity was noted in any other animals; normal motor activity was recorded.
In a five-day rat toxicology study, male and female rats were challenged with twice-daily doses of FAS 31 from 0 to 500 mg/Kg ip or orally. No abnormal behavior or distress was noted attributable to FAS 31. All chemistry and hematology studies were within normal limits.
The multiple successful mouse efficacy trials in human ovarian cancer cell lines, showing 80% reduction in SKOV-3 tumor xenografts, and the combination of toxicity, maximum tolerated dose, bioavailability and pK studies lead to the conclusions that FAS31 is efficacious against ovarian cancer tumors, is non-toxic and is a viable pharmacological candidate for anti-cancer therapy.
In a new study published in Cell Stem Cell, a team of researchers have demonstrated, using fat cells derived from human stem cells, that individual genetic variation can be used to predict whether the TZD rosiglitazone will produce the unwanted side effect of increasing cholesterol levels in certain individuals.READ MORE