Beyond the widespread physiological implications of the estrogens in human cells, there is a central role of the estrogens in the cancer pathway. In this special issue, we will review the molecular influence of the different subtypes of estrogen receptors as a promoter or as an inhibitor in the cancer pathogenesis.
We can say that there is a relation between the estrogen levels and his exposure time with the development risk of breast and endometrium cancer, however, in different neoplasm such as ovarian cancer, works as a protector factor. Using the aforementioned as a premise, different researches have shown prognostic value in breast cancer, lung cancer, mesothelioma, among others. The heterogeneous effect of estrogens in tumoral cells could lie in the specific estrogen receptor (ER) subtype that is stimulated. Some examples of the influence of ER in cancer are: 1) The ERα and his promoting effects in breast cancer, although the role of the β subtype of this receptor still uncertain, elucidating his paper in the pathogenesis of breast cancer still remains relevant given their common prevalence in these tumor cells and some evidences that natural or synthetic ERβ-selective estrogens may lack breast cancer-promoting properties exhibited by estrogens in hormone replacement regimens and may be useful for chemoprevention of breast cancer. 2) In healthy lung tissue, ERβ is highly expressed in pneumocytes and in the bronchial epithelial cells, and is required for the maintenance of the extracellular matrix of the lung, as well as in healthy lung tissue, ER are consistently found in lung cancer tissues and cell lines, especially adenocarcinoma, and mostly in the form of the ERβ. Estrogen has been reported to adversely affect the prognosis of lung cancer patients. However, there are several studies with conflicting results about the effect of estrogen on the risk and/or survival of lung cancer. 3) Finally, our research group found recently that high and moderate expression of ERβ in advanced clinical stage malignant pleural mesothelioma was associated with a tendency of higher overall survival and better response to chemotherapy treatment resulting in longer progression-free survival. Some studies also have demonstrated that using a selective agonist of ERβ decreases the growth of malignant pleural mesothelioma cells in both in vitro and in murine models, as well as an increase in the sensitivity to the anti-tumor treatment.
This varied interaction between different estrogen receptors and their effects on different types of cancer makes it an exciting topic that leaves a niche of knowledge to understand and redesign new therapeutic strategies against molecular mediators to assist in cancer treatment and disease management.