Antitumor activity of a new cholesterol derivative (24-ethyl-cholestane- 3β, 5α,6α-triol) in solid tumors

Abstract

e13541 Oxysterols are oxygenated derivatives of cholesterol. They have nuclear receptors and have been shown to pass cell membranes and the blood-brain barrier at a faster rate than cholesterol itself. In addition, oxysterols have been ascribed a number of important roles in connection with cholesterol turnover, atherosclerosis, apoptosis, and necrosis. Oxysterols have been shown to have antitumor effects on experimental models. These compounds however may be toxic and to our knowledge, although some derivatives have been tested in animals, none have reached the clinical level. 24-ethyl-cholestane- 3β,5α,6α-triol is a new oxysterol developed in our lab. An oral form of this compound has been tested in mice and rats and has shown neither acute nor chronic toxicity. It has also been tested on animal tumor models and on human cancer xenografts. The results of these tests were very promising showing an anti-tumor activity on a panel of tumor cell lines. Our experiments on humans have shown no toxicity for this drug. Many patients with a variety of solid tumors all of whom have received many lines of chemotherapy and considered refractory to any conventional therapy have received this new drug. We observed in most of these patients a rapid and dramatic improvement in their quality of life and a fast pain control. Some patients could stop taking high doses of opioids within 1 or 2 days. A high rate of clinical benefit has also been observed in a variety of solid tumors including lung, breast, pancreatic, ovarian and uterine cancers, associated in some cases with a sharp decrease in tumor markers. Some patients with brain tumors (glioblastomas) have also responded to this therapy. No significant financial relationships to disclose.