Hormonal therapy in oncology is hormone therapy for cancer and is one of the major modalities of medical oncology (pharmacotherapy for cancer), others being cytotoxic chemotherapy and targeted therapy (biotherapeutics). It involves the manipulation of the endocrine system through exogenous or external administration of specific hormones, particularly steroid hormones, or drugs which inhibit the production or activity of such hormones (hormone antagonists). Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing, or even undergo cell death. Surgical removal of endocrine organs, such as orchiectomy and oophorectomy can also be employed as a form of hormonal therapy.
Hormonal therapy is used for several types of cancers derived from hormonally responsive tissues, including the breast, prostate, endometrium, and adrenal cortex. Hormonal therapy may also be used in the treatment of paraneoplastic syndromes or to ameliorate certain cancer- and chemotherapy-associated symptoms, such as anorexia. Perhaps the most familiar example of hormonal therapy in oncology is the use of the selective estrogen-response modulator tamoxifen for the treatment of breast cancer, although another class of hormonal agents, aromatase inhibitors, now have an expanding role in that disease.
Inhibitors of hormone synthesis
One effective strategy for starving tumor cells of growth- and survival-promoting hormones is to use drugs which inhibit the production of those hormones in their organ of origin.
Aromatase inhibitors
Aromatase inhibitors are an important class of drugs used for the treatment of breast cancer in postmenopausal women. At menopause, estrogen production in the ovaries ceases, but other tissues continue to produce estrogen through the action of the enzyme aromatase on androgens produced by the adrenal glands. When the action of aromatase is blocked, estrogen levels in post-menopausal women can drop to extremely low levels, causing growth arrest and/or apoptosis of hormone-responsive cancer cells.
Letrozole and anastrozole are aromatase inhibitors which have been shown to be superior to tamoxifen for the first-line treatment of breast cancer in postmenopausal women. Exemestane is an irreversible "aromatase inactivator" which is superior to megestrol acetate for treatment of tamoxifen-refractory metastatic breast cancer, and does not appear to have the osteoporosis-promoting side effects of other drugs in this class.
Aminoglutethimide inhibits both aromatase and other enzymes critical for steroid hormone synthesis in the adrenal glands. It was formerly used for breast cancer treatment, but has since been replaced by more selective aromatase inhibitors. It can also be used for the treatment of hyperadrenocortical syndromes, such as Cushing's syndrome and hyperaldosteronism in adrenocortical carcinoma.
GnRH analogues
Analogs of gonadotropin-releasing hormone (GnRH) can be used to induce a chemical castration, that is, complete suppression of the production of estrogen and progesterone from the female ovaries, or complete suppression of testosterone production from the male testes. This is due to a negative feedback effect of continuous stimulation of the pituitary gland by these hormones. Leuprorelin and goserelin are GnRH analogs which are used primarily for the treatment of hormone-responsive prostate cancer. Because the initial endocrine response to GnRH analogs is actually hypersecretion of gonadal steroids, hormone receptor antagonists such as flutamide are typically used to prevent a transient boost in tumor growth.
Hormone receptor antagonists
Hormone receptor antagonists bind to the normal receptor for a given hormone and prevent its activation. The target receptor may be on the cell surface, as in the case of peptide and glycoprotein hormones, or it may be intracellular, as in the case of steroid hormone receptors.