Estrogen-dependent signaling pathways and their role in the tumor progression: progress and perspectives

Over the last forty years antiestrogen tamoxifen belongs to the most effective antitumor drugs widely used in the treatment of breast cancer, however, the efficiency of tamoxifen therapy is often limited by development of tumor hormonal resistance. The study of the mechanism of hormonal resistance led to the significant progress in the insight in signaling pathways respondent for the cancer cell growth in the absence of estrogen. In the review we have analyzed the recent data including our results obtained in the N. N. Blokhin RCRC, concerned with the study of the new aspects of hormonal resistance – the involvement of hypoxia-dependent HIF-1α / VEGF pathway, epithelial-mesenchymal transition and mTOR / AMPK in the formation of estrogen-independent phenotype. Some of the signaling proteins are considered as the potential targets for the therapy of the estrogen-resistant breast cancer.