Hyperplasie bénigne et cancer de la prostate : hormones stéroïdiennes et facteurs de croissance

Abstract

Statistics concerning the incidence of benign prostatic hyperplasia and cancer in industrialized countries are alarming : between 50 and 80 years of age, 50 % to 90 % of men develop an hyperplastic prostate and 30 % of them will have to undergo surgery ; moreover, one man out of eleven suffers from prostate cancer and the chances of cure, even with the most advanced endocrine therapies, are limited. This is mainly due to the fact that the relapse of most tumors is caused by androgen- independent cell proliferation. In the present review, we will consider androgen-dependent and -independent prostatic epithelial cells, with respect to the actual therapies used for prostate cancer and regarding the fundamental questions now being addressed in the field of prostate physiopathology. The beneficial effects of castration and of estrogen administration observed in the forties were the basis of the endocrine therapies in current use. Chemical castration with LH-RH analogs is gradually replacing surgical castration while anti-androgens and inhibitors of 5alpha-reductase are administered to prevent, respectively, the binding of hormones, including adrenal androgens, to their specific receptors and the formation of the active metabolite, dihydrotestosterone. Up to now, investigators have failed to correlate androgen receptors with the response of patients to endocrine therapies. Further studies at the molecular level are required to understand the mechanisms underlying hormone dependency or independency. The major problem of tumor relapse after endocrine therapies remains unsolved and limits the clinicians to non-specific treatments such as radio- and chemotherapies. It has led to a whole new field of fundamental research related to prostate growth, namely on the role of prostatic stroma, genetic rearrangement, rate of cell death and, particularly, on the role of known growth factors and/or of novel prostatic factors as well as their receptors and related protein-tyrosine-kinases and oncogenes. These avenues appear very promising. There is more and more indications that these research efforts will lead to the development of new diagnostic methods and of specific therapies in the near future.