Immunomodulatory effects of anti-estrogenic drugs

Abstract

<jats:title>Immunomodulatory effects of anti-estrogenic drugs</jats:title><jats:p>There are substantial experimental, epidemiological and clinical evidences that show that breast cancer pathology is influenced by endogenous estrogens. This knowledge is the foundation upon which endocrine deprivation therapy has been developed as a major modality for the management of breast cancer. Tamoxifen, which functions as a competitive partial agonist-inhibitor of estrogen at its receptor, has been widely used for more than three decades for adjuvant endocrine treatment in breast cancer. Currently, other effective drugs for endocrine therapy include raloxifene, different aromatase inhibitors (particularly third-generation agents) and luteinizing hormone-releasing hormone agonists. In recent years, a growing body of evidence suggests that these drugs can also act as immune modulators by altering the function of various leukocytes and the release of different cytokines. Moreover, there is evidence that anti-estrogens may prove to be beneficial in the treatment or prevention of some autoimmune diseases due to their effects on immune function. However, their immunopharmacological aspects in the present state of knowledge are not precisely comprehensible. Only a clear pathophysiological understanding could lead to an efficient strategy for breast cancer prevention and decrease in the mortality due to this disease.</jats:p>

Estrogen biology: New insights into GPER function and clinical opportunities

“…Estrogen and, as more recently demonstrated, drugs commonly used as “anti-estrogens”, exert multiple effects upon the development and function of the immune system (Ray and Ficek, 2012; Bonds and Midoro-Horiuti, 2013; Sakiani et al, 2013), as exemplified by the developmental effects of estrogen in estrogen-promoted atrophy of the thymus during pregnancy (Pernis, 2007). Expression of GPER in multiple immune cells, including B and T cells, monocytes/macrophages and neutrophils, suggested that some estrogenic effects in the immune system could be mediated by GPER (Wang et al, 2008a; Blasko et al, 2009; Rettew et al, 2010; Cabas et al, 2013).…”

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…A recent in vivo study (using ApoE −/− and C57BL/6 mice, Table 4 [82], [83], [84], [85], [86], [87], [88], [89]) has recorded the detrimental role of EGFR in the pathogenesis of obesity-related nephropathy [90]. In a clinical study, after analyzing 100 postmenopausal breast cancer specimens, Xuan et al [91] found that tamoxifen resistance was associated with obesity, and EGFR expression was higher in tamoxifen resistance cases compared to tamoxifen sensitive group (Table 5 [ 32], [92], [93], [94]). Overall, the status of EGFR in the lipogenic environment is intricate.…”

“…This drug competes for the tyrosine kinase domain of EGFR and blocks its phosphorylation, which inhibits cellular signal transduction Tamoxifen [93] Selective estrogen receptor modulator (SERM)…”

International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators

“…Estrogen (Bonds and Midoro-Horiuti, 2013;Sakiani et al, 2013), as well as therapeutic "antiestrogens," such as tamoxifen and raloxifene (Ray and Ficek, 2012), exerts diverse effects upon multiple aspects of immune system development and function. A role for GPER in E2-mediated thymic atrophy (Pernis, 2007) was first suggested through the use of ERa, ERb, and GPER knockout mice (Wang et al, 2008a), where ERa expression was required for the early developmental blockage of thymocyte development and GPER expression was necessary for apoptosis of T-cell receptor double-positive thymocytes.…”