Potential of Selective Estrogen Receptor Modulators as Treatments and Preventives of Breast Cancer

Abstract

Estrogen plays vital roles in human health and diseases. Estrogen mediates its actions almost entirely by binding to estrogen receptors (ER), alpha and beta which further function as transcription factors. Selective estrogen receptor modulators (SERMs) are synthetic molecules which bind to ER and can modulate its transcriptional capabilities in different ways in diverse estrogen target tissues. Tamoxifen, the prototypical SERM, is extensively used for targeted therapy of ER positive breast cancers and is also approved as the first chemo-preventive agent for lowering breast cancer incidence in high risk women. The therapeutic and preventive efficacy of tamoxifen was initially proven by series of experiments in the laboratory which laid the foundation of its clinical use. Unfortunately, use of tamoxifen is associated with de-novo and acquired resistance and some undesirable side effects. The molecular study of the resistance provides an opportunity to precisely understand the mechanism of SERM action which may further help in designing new and improved SERMs. Recent clinical studies reveal that another SERM, raloxifene, which is primarily used to treat post-menopausal osteoporosis, is as efficient as tamoxifen in preventing breast cancers with fewer side effects. Overall, these findings open a new horizon for SERMs as a class of drug which not only can be used for therapeutic and preventive purposes of breast cancers but also for various other diseases and disorders. Major efforts are therefore directed to make new SERMs with a better therapeutic profile and fewer side effects.

Noninvasive Detection of Activating Estrogen Receptor 1 (ESR1) Mutations in Estrogen Receptor–Positive Metastatic Breast Cancer

“…Although development of novel therapeutics for the treatment of breast cancers is continually improving, innate and acquired resistance to these drugs remains a challenge. The tumor microenvironment has been suggested as a major factor in conferring innate resistance to cancer therapies (1 ), whereas a large proportion of patients develop resistance while receiving systemic antiestrogens such as tamoxifen or estrogen deprivation therapies such as aromatase inhibitors (AIs) (2)(3)(4)(5). A number of mechanisms, including activation of cell survival, cell stress, and cell signaling pathways, have been proposed as drivers of acquired resistance (6,7 ).…”

Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (−)-Epigallocatechin-3-gallate and Luteolin

“…Chemoprevention strategies have achieved success in colorectal cancer using nonsteroidal anti-inflammatory drugs (2,3) and breast cancer using tamoxifen (reviewed in Refs. 4,5). Like chemotherapy, combinatorial chemoprevention strategies also have shown early success (6 -10), although such strategies have not been pursued as aggressively as in chemotherapy.…”

Drug Transporter-independent Liver Cancer Cell Killing by a Marine Steroid Methyl Spongoate via Apoptosis Induction

“…These hormones mediate their actions almost entirely by binding to their respective receptors and then function as transcription factors. Their antagonists, for example, tamoxifen, elicit significant anticancer effects by blocking the binding of hormones to their receptors in those steroid hormone-dependent cancers (23,24). To clarify whether the anticancer effect of MESP relies on the steroid hormone signaling, we evaluated its proliferation inhibition against a panel of breast cancer cells expressing or not expressing estrogen receptors and prostate cancer cells expressing or not expressing androgen receptors.…”