ABSTRACT
Endocrine therapies available to block steroid hormone receptor-mediated tumor growth are based on two principles: ligand depletion and receptor blockade. Ligand depletion can be achieved either by removal of steroid-producing glands or by inhibition of steroid biosynthesis. Estrogen receptors can be blocked either with selective estrogen receptor modulators or by a new class of compounds, the pure antiestrogens. The physiological effects of progesterone are mediated by two nuclear receptor proteins, termed A and B, which arise from a single gene and act as ligand-activated transcription factors to regulate the expression of target genes. Progesterone antagonists exert a strong tumor-inhibiting effect in a panel of hormone-dependent rodent mammary tumor models. Quantitative light and electron microscopic data from the experiments indicate that the antitumor action of antiprogestins is accompanied by the initiation of terminal differentiation leading to apoptotic cell death. Growth inhibition studies in breast cancer cell lines can be used to screen antiprogestins for antiproliferative activity.
