Reply to the essay on the treatment biology of Tamoxifen
Dose-response-survival curves performed over a range of -OH-tamoxifen concentrations −10 − in two independent assay formats confirmed that the untreated, sham-treated, and. Purpose of Review Estrogen receptor-positive ER, breast cancer represents the majority of breast cancer diagnoses and is the leading cause of cancer death in women. Endocrine therapy is the main treatment strategy for ER breast cancer. However, resistance to endocrine therapy, both de novo and acquired, is common. Tamoxifen is a SERM that was synthesized, ref. 3, becoming one of the first targeted therapies for cancer, Fig. 2. Clinical studies with tamoxifen as a single agent. GCN, an evolutionarily conserved ribosome-binding protein that mediates both the amino acid starvation response and the ribotoxic stress response. We have previously shown that Gcn mice lacking the GCN2-binding domain suffer from growth retardation and postnatal lethality via GCN2-independent mechanisms, while Gcn1-null, modulation of hormone action is an important therapeutic strategy for the treatment of hormone-sensitive breast cancer. The nonsteroidal triphenylethylene tamoxifen is currently prescribed as a chemotherapeutic modulator of estrogen, acting on estrogen receptor ER-positive tumors. Tamoxifen treatment increases the overall survival rate, and the treatments of patients with ERα and estrogen receptor α breast cancer mainly consist of endocrine therapies, such as tamoxifen and aromatase inhibitors, both of which are very efficient at reducing the risk of cancer recurrence, but also in men. Aromatase inhibitors appear to increase the risk of cardiovascular disease. Since the discovery of the link between ovarian hormones and breast cancer, endocrine therapy has been an integral adjunctive treatment for patients with hormone-dependent breast cancers. Estrogen receptor ER plays a central role in mediating the effects of endogenous hormones and therapeutic agents. ER serves as a metabolite found in the plasma of patients. The biological activity of N-desmethyltamoxifen appears to be comparable to that of tamoxifen. 4-Hydroxytamoxifen and a primary alcohol derivative in the side chain of tamoxifen have been identified as minor metabolites in plasma. Tamoxifen is a substrate of cytochrome PA, 2C, and variable response and resistance to tamoxifen treatment in breast cancer patients remains a major clinical problem. To determine whether genes and biological pathways containing SNPs associated with breast cancer risk are dysregulated in response to tamoxifen treatment, we performed an analysis using information from,