Estrogen Receptors, Antiestrogens, and Non-Small Cell Lung Cancer

This review considers data on expression of different types of estrogen receptors (ER alpha and ER beta) in in vitro cultured cells of non-small cell lung cancer and also in human and animal lung tumors. Estrogens are shown to play an important role in genesis and development of non-small cell lung cancer because the estrogen-stimulated cell proliferation as well as antiestrogen-caused inhibition of proliferation occurred only in the cells expressing different types of estrogen receptors. In general, the situation is similar to that observed in breast cancer, but in the cells of non-small cell lung cancer not ER alpha are expressed in more than half of cases but ER beta. Just estrogen receptors beta play the crucial role in inducing cell proliferation in response to estrogens, and ER beta is a prognostic marker of a favorable course of non-small cell lung cancer. Data on the interactions between ER and EGFR signaling pathways, as well as on the additive antitumor effect of antiestrogens (tamoxifen and fulvestrant) combined with tyrosine kinase inhibitors (gefitinib, erlotinib, and vandetanib) are considered. The review also includes data on the influence of estrogens on genesis and development of lung cancer in humans and animals and the frequency of ER alpha and ER beta expression in non-small cell lung cancer in tissues from patients of the two sexes. Problems of quantitative determination of alpha and beta estrogen receptors in the tumor cells are also discussed.