STEROIDS AND HORMONO-DEPENDANT DISEASES

Prostate and breast cancers represent approximately 30% of all cancers in men and women, whereas osteoporosis and cardiovascular diseases are the main health problems associated with menopause. A common feature among these diseases is the role played by androgens and estrogens.

My research program deals with the basic mechanisms which underly these pathologies and it extends to the development of new drugs and the evaluation of their therapeutic efficacy in clinical trials. As a result of the discovery made in the Laboratory of Molecular Endocrinology on the major role played by androgens and estrogens synthesized in target peripheral tissues, my research program aims at identifying the genes responsible for the conversion of dehydroepiandrosterone (DHEA) - the adrenal precursor - into androgens and/or estrogens in each cell type of the prostate, the mammary gland, the bone, the cardiovascular system and the skin. To determine the role of each of these genes, models of normal and cancer cells are used in vitro. We also conduct in vivo studies in nude or transgenic mice models to determine the role of these hormones and the consequences of the inhibition of their action.

To obtain a maximal blockade of these hormones in diseases stimulated by these steroids, we have synthesized inhibitors of enzymes necessary for their formation. We have also synthesized inhibitors of steroid hormone receptors for the treatment of prostate and breast cancers. EM-800, a pure antiestrogen with high activity, has been entirely developed in our Laboratory. It is now being tested in a phase III international clinical study.

As for osteoporosis and cardiovascular diseases linked to menopause, we are developing new drugs that prevent bone loss, decrease circulating levels of lipids and decrease the incidence of breast and uterine cancers.

Our fundamental research in molecular biology, genetics, biochemistry and cell biology represent 80% of our activities.

These projects are supported by the Medical Research Council Group in Molecular Endocrinology.

Bélanger A, Labrie C, Labrie F (1997) (s)-(+)-4-[7-(2,2-dimethyl-1-oxopropoxy)-4-methyl-2-[4-[2-(1-piperidinyl)-ethoxy]-
2H-1-benzopyran-3yl]-phenyl 2,2-dementhylpropanoate (EM-800) : a highly potent, specific, and orally active nonsteroidal antiestrogen. Journal of Medicinal Chemistry 40 (14) 2117-2122.