ESTROGEN GROWTH-FACTOR CROSS-TALK IN BREAST-CARCINOMA - A SPECIFIC TARGET FOR NOVEL ANTIESTROGENS

Breast cancer cells express receptors for and are sensitive to a varie ty of steroids, polypeptide hormones and growth factors; the blocking of and/or the interference with their biochemical pathways could repre sent a new approach to breast tumour therapy. Antioestrogens achieve s uch a goal by competing with oestradiol for binding to the oestrogen r eceptors through which intracellular effects of the hormone are mediat ed. Tamoxifen has undergone the most extensive clinical evaluations an d represents the treatment of choice for the endocrine management of b reast cancer. Nevertheless, it is well known that tamoxifen retains ag onist activity both in vitro and in vivo. To circumvent this disadvant age, new molecules with steroid-like structure, represented by ICI 164 ,384 and ICI 182,780, have been synthesized. in this review, Alessandr a de Cupis and Roberto Favoni review data about the cross-talk between the two major families of breast cancer growth regulators: oestrogens and growth factors, focusing on the use of nonsteroidal antioestrogen s and the new generation of steroidal antioestrogens as possible speci fically targeted inhibitors of breast tumour proliferation.