TAILIEUCHUNG - Chapter 080. Cancer Cell Biology and Angiogenesis (Part 10)

Estrogen receptors (ERs) and androgen receptors, members of the steroid hormone family of nuclear receptors, are targets of inhibition by drugs used to treat breast and prostate cancers, respectively. Tamoxifen, a partial agonist and antagonist of ER function, can mediate tumor regression in metastatic breast cancer and can prevent disease recurrence in the adjuvant setting, saving thousands of lives each year. Tamoxifen binds to the ER and modulates its transcriptional activity, inhibiting activity in the breast but promoting activity in bone and uterine epithelium. Selective estrogen receptor modulators (SERMs) have been developed with the hope of a more beneficial. | Chapter 080. Cancer Cell Biology and Angiogenesis Part 10 Estrogen receptors ERs and androgen receptors members of the steroid hormone family of nuclear receptors are targets of inhibition by drugs used to treat breast and prostate cancers respectively. Tamoxifen a partial agonist and antagonist of ER function can mediate tumor regression in metastatic breast cancer and can prevent disease recurrence in the adjuvant setting saving thousands of lives each year. Tamoxifen binds to the ER and modulates its transcriptional activity inhibiting activity in the breast but promoting activity in bone and uterine epithelium. Selective estrogen receptor modulators SERMs have been developed with the hope of a more beneficial modulation of ER activity . antiestrogenic activity in the breast uterus and ovary but estrogenic for bone brain and cardiovascular tissues. Aromatase inhibitors which block the conversion of androgens to estrogens in breast and subcutaneous fat tissues have demonstrated Apoptosis Tissue homeostasis requires a balance between the death of aged terminally differentiated cells and their renewal by proliferation of committed progenitors. Genetic damage to growth-regulating genes of stem cells could lead to catastrophic results for the host as a whole. However genetic events causing activation of oncogenes or loss of tumor suppressors which would be predicted to lead to unregulated cell proliferation instead activate signal transduction pathways that block aberrant cell proliferation. These pathways can lead to programmed cell death apoptosis or irreversible growth arrest senescence . Much as a panoply of intra- and extracellular signals impinge upon the core cell cycle machinery to regulate cell division so too these signals are transmitted to a core enzymatic machinery that regulates cell death and survival. Apoptosis is induced by two main pathways Fig. 80-5 . The extrinsic pathway of apoptosis is activated by cross-linking members of the tumor necrosis

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