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Hormonal therapy (oncology)
Encyclopedia
Hormonal therapy is one of the major modalities of medical treatment for cancer, others being cytotoxic chemotherapy
and targeted therapy
(biotherapeutics). It involves the manipulation of the endocrine system
through exogenous administration of specific hormone
s, particularly steroid hormone
s, or drugs which inhibit the production or activity of such hormones (hormone antagonist
s). 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 cancer
s derived from hormonally responsive tissues
, including the breast
, prostate
, endometrium
, and adrenal cortex
. Hormonal therapy may also be used in the treatment of paraneoplastic syndrome
s or to ameliorate certain cancer- and chemotherapy
-associated symptom
s, 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 inhibitor
s, now have an expanding role in that disease.
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.
s 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 androgen
s produced by the adrenal gland
s. 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
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 gland
s. 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) 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. Leuprolide
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.
receptors.
Selective estrogen receptor modulators (SERM's) are an important class of hormonal therapy agents which act as antagonists of the estrogen receptor and are used primarily for the treatment and chemoprevention of breast cancer
. Some members of this family, such as tamoxifen
, are actually partial agonist
s, which can actually increase estrogen receptor signalling in some tissues, such as the endometrium
. Tamoxifen is currently first-line treatment for nearly all pre-menopausal
women with hormone receptor-positive breast cancer. Raloxifene
is another partial agonist SERM which does not seem to promote endometrial cancer
, and is used primarily for chemoprevention of breast cancer in high-risk individuals, as well as to prevent osteoporosis
. Toremifene
and fulvestrant
are SERM's with little or no agonist activity, and are used for treatment of metastatic
breast cancer.
, blocking the growth- and survival-promoting effects of testosterone
on certain prostate cancer
s. Flutamide
and bicalutamide
are antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy, or in the initial few weeks of GnRH analog therapy.
While most hormonal therapy strategies seek to block hormone signalling to cancer cells, there are some instances in which supplementation with specific hormone agonists may have a growth-inhibiting, or even cytotoxic effect on tumor cells. Because many hormones can produce antagonism and feedback inhibition of the synthesis of other hormones, there is significant overlap between this concept and those discussed above.
s (progesterone
-like drugs) such as megestrol
and medroxyprogesterone
have been used for the treatment of hormone-responsive, advanced breast cancer
, endometrial cancer
, and prostate cancer
. Progestins are also used in the treatment of endometrial hyperplasia
, a precursor to endometrial adenocarcinoma. The exact mechanism of action of these hormones is unclear, and may involve both direct effect on the tumor cells (suppression of estrogen receptor levels, alteration of hormone metabolism, direct cytotoxicity) and indirect endocrine effects (suppression of adrenal androgen production and plasma estrone sulfate formation).
(testosterone
-like drug) Fluoxymesterone
is occasionally used for the treatment of advanced breast cancer
. The mechanism of the anticancer effects of this androgen in breast cancer are unclear, but may be analogous to those of progestins.
agonist Diethylstilbestrol
(DES) is occasionally used to treat prostate cancer
through suppression of testosterone production. It was previously used in the treatment of breast cancer
, but has been replaced by more effective and less toxic agents. Estrace is an estrogen which was also formerly used for anti-androgen
therapy of prostate cancer.
is an analog of the peptide hormone somatostatin
, which inhibits the production of the growth hormone as well as numerous peptide hormones of the gastrointestinal system, including insulin
, glucagon
, pancreatic polypeptide
, gastic inhibitory polypeptide, and gastrin
. Octreotide is used for suppression of the hormonal syndromes which accompany several pancreatic islet cell tumors, including the Zollinger-Ellison syndrome
of gastrinoma
and the chronic hypoglycemia
of insulinoma
. It is also effective in suppression of the carcinoid syndrome
, caused by advanced or extra-gastrointestinal carcinoid
tumors. Octreotide may also be used for treatment of severe diarrhea caused by 5-fluorouracil chemotherapy
or radiation therapy
.
or radiation therapy
are also possible. Surgical castration
, or removal of the testes in males and ovaries in females, have been widely used in the past to treat hormone-responsive prostate cancer
and breast cancer
respectively. However, these invasive methods have been widely supplanted by the use of GnRH agonists, and other forms of pharmacologic castration.
There are still situations in which surgical castration may be beneficial such as in special cases for women with high risk BRCA mutation
s.
Hormonal stimulation of the immune system with interferon
s and cytokines has been used to treat specific cancers, including renal cell carcinoma
and melanoma
.
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
and targeted therapy
Targeted therapy
Targeted therapy is a type of medication that blocks the growth of cancer cells by interfering with specific targeted molecules needed for carcinogenesis and tumor growth, rather than by simply interfering with rapidly dividing cells...
(biotherapeutics). It involves the manipulation of the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...
through exogenous administration of specific hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s, particularly steroid hormone
Steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
s, or drugs which inhibit the production or activity of such hormones (hormone antagonist
Hormone antagonist
For the use of hormone antagonists in cancer, see hormonal therapy A Hormone antagonist is a specific type of receptor antagonist which acts upon hormones....
s). Because steroid hormones are powerful drivers of gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
in certain cancer cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, 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
Oophorectomy
Oophorectomy is the surgical removal of an ovary or ovaries. The surgery is also called ovariectomy, but this term has been traditionally used in basic science research describing the surgical removal of ovaries in laboratory animals...
can also be employed as a form of hormonal therapy.
Hormonal therapy is used for several types of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
s derived from hormonally responsive tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
, including the breast
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, prostate
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
, endometrium
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
, and adrenal cortex
Adrenocortical carcinoma
Adrenocortical carcinoma, also adrenal cortical carcinoma and adrenal cortex cancer, is an aggressive cancer originating in the cortex of the adrenal gland. Adrenocortical carcinoma is a rare tumor, with incidence of 1-2 per million population annually...
. Hormonal therapy may also be used in the treatment of paraneoplastic syndrome
Paraneoplastic syndrome
A paraneoplastic syndrome is a disease or symptom that is the consequence of the presence of cancer in the body, but is not due to the local presence of cancer cells. These phenomena are mediated by humoral factors excreted by tumor cells or by an immune response against the tumor...
s or to ameliorate certain cancer- and chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
-associated symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s, such as anorexia
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
. Perhaps the most familiar example of hormonal therapy in oncology
Oncology
Oncology is a branch of medicine that deals with cancer...
is the use of the selective estrogen-response modulator tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
for the treatment of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, although another class of hormonal agents, aromatase inhibitor
Aromatase inhibitor
Aromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....
s, 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 inhibitorAromatase inhibitor
Aromatase inhibitors are a class of drugs used in the treatment of breast cancer and ovarian cancer in postmenopausal women. AIs may also be used off-label to treat or prevent gynaecomastia in men....
s are an important class of drugs used for the treatment of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
in postmenopausal
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
women. At menopause, estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
production in the ovaries ceases, but other tissues continue to produce estrogen through the action of the enzyme aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
on androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
s produced by the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s. 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
Letrozole
Letrozole is an oral non-steroidal aromatase inhibitor for the treatment of hormonally-responsive breast cancer after surgery.Estrogens are produced by the conversion of androgens through the activity of the aromatase enzyme...
and anastrozole
Anastrozole
Anastrozole is an aromatase-inhibiting drug approved for treatment of breast cancer after surgery, as well as for metastasis in both pre and post-menopausal women. The severity of breast cancer is increased by estrogen, as sex hormones cause hyperplasia, and differentiation at estrogen receptor...
are aromatase inhibitors which have been shown to be superior to tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
for the first-line treatment of breast cancer in postmenopausal women. Exemestane
Exemestane
Exemestane is a drug used to treat breast cancer. It is a member of the class of drugs known as aromatase inhibitors. Some breast cancers require estrogen to grow. Those cancers have estrogen receptors , and are called ER-positive. They may also be called estrogen-responsive,...
is an irreversible "aromatase inactivator" which is superior to megestrol
Megestrol
Megestrol is a progesterone derivative with antineoplastic properties used in the treatment of advanced carcinoma of the breast and endometrium. When given in relatively high doses, Megestrol can substantially increase appetite in most individuals, even those with advanced cancer...
for treatment of tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
-refractory metastatic breast cancer, and does not appear to have the osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
-promoting side effects of other drugs in this class.
Aminoglutethimide
Aminoglutethimide
Aminoglutethimide is an anti-steroid drug marketed under the tradename Cytadren by Novartis around the world. It blocks the production of steroids derived from cholesterol and is clinically used in the treatment of Cushing's syndrome and metastatic breast cancer...
inhibits both aromatase
Aromatase
Aromatase is an enzyme responsible for a key step in the biosynthesis of estrogens. It is a member of the cytochrome P450 superfamily , which are monooxygenases that catalyze many reactions involved in steroidogenesis. In particular, aromatase is responsible for the aromatization of androgens into...
and other enzymes critical for steroid hormone synthesis in the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
s. It was formerly used for breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
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
Cushing's syndrome
Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone or CRH...
and hyperaldosteronism
Conn's syndrome
Primary aldosteronism, also known as primary hyperaldosteronism, is characterized by the overproduction of the mineralocorticoid hormone aldosterone by the adrenal glands., when not a result of excessive renin secretion. Aldosterone causes increase in sodium and water retention and potassium...
in adrenocortical carcinoma
Adrenocortical carcinoma
Adrenocortical carcinoma, also adrenal cortical carcinoma and adrenal cortex cancer, is an aggressive cancer originating in the cortex of the adrenal gland. Adrenocortical carcinoma is a rare tumor, with incidence of 1-2 per million population annually...
.
GnRH analogs
Analogs of gonadotropin-releasing hormoneGonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
(GnRH) can be used to induce a chemical castration
Chemical castration
Chemical castration is the administration of medication designed to reduce libido and sexual activity, usually in the hope of preventing rapists, child molesters and other sex offenders from repeating their crimes...
, that is, complete suppression of the production of estrogen and progesterone from the female ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...
, or complete suppression of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
production from the male testes. This is due to a negative feedback effect of continuous stimulation of the pituitary gland by these hormones. Leuprolide
Leuprolide
Leuprorelin or leuprolide acetate is a GnRH analog. Proper Sequence: Pyr-His-Trp-Ser-Tyr-D-Leu-Leu-Arg-Pro-NHEt - Mode of action:Leuprolide acts as an agonist at pituitary GnRH receptors...
and goserelin
Goserelin
Goserelin acetate is an injectable gonadotropin releasing hormone superagonist , also known as a luteinizing hormone releasing hormone agonist. Structurally, it is a decapeptide...
are GnRH analogs which are used primarily for the treatment of hormone-responsive prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
. Because the initial endocrine response to GnRH analogs is actually hypersecretion of gonadal steroids, hormone receptor antagonists such as flutamide
Flutamide
Flutamide is an oral nonsteroidal antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer...
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 recepetor 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 hormoneSteroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into five groups by the receptors to which they bind: glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens...
receptors.
Selective estrogen receptor modulators
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. Some members of this family, such as tamoxifen
Tamoxifen
Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...
, are actually partial agonist
Partial agonist
Partial agonists bind and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist...
s, which can actually increase estrogen receptor signalling in some tissues, such as the endometrium
Endometrium
-Function:The endometrium is the innermost glandular layer and functions as a lining for the uterus, preventing adhesions between the opposed walls of the myometrium, thereby maintaining the patency of the uterine cavity. During the menstrual cycle or estrous cycle, the endometrium grows to a...
. Tamoxifen is currently first-line treatment for nearly all pre-menopausal
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
women with hormone receptor-positive breast cancer. Raloxifene
Raloxifene
Raloxifene is an oral selective estrogen receptor modulator that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast...
is another partial agonist SERM which does not seem to promote endometrial cancer
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
, and is used primarily for chemoprevention of breast cancer in high-risk individuals, as well as to prevent osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
. Toremifene
Toremifene
Toremifene citrate is an oral selective estrogen receptor modulator which helps oppose the actions of estrogen in the body. Licensed in the United States under the brand name Fareston, toremifene citrate is FDA-approved for use in advanced breast cancer...
and fulvestrant
Fulvestrant
Fulvestrant, also known as ICI 182,780, is a drug treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. It is an estrogen receptor antagonist with no agonist effects, which works both by down-regulating and...
are SERM's with little or no agonist activity, and are used for treatment of metastatic
Metastasis
Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research...
breast cancer.
Antiandrogens
Antiandrogens are a class of drug which bind and inhibit the androgen receptorAndrogen receptor
The androgen receptor , also known as NR3C4 , is a type of nuclear receptor that is activated by binding of either of the androgenic hormones testosterone or dihydrotestosterone in the cytoplasm and then translocating into the nucleus...
, blocking the growth- and survival-promoting effects of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
on certain prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
s. Flutamide
Flutamide
Flutamide is an oral nonsteroidal antiandrogen drug primarily used to treat prostate cancer. It competes with testosterone and its powerful metabolite, dihydrotestosterone for binding to androgen receptors in the prostate gland. By doing so, it prevents them from stimulating the prostate cancer...
and bicalutamide
Bicalutamide
Bicalutamide is an oral non-steroidal anti-androgen used in the treatment of prostate cancer and hirsutism...
are antiandrogens which are frequently used in the treatment of prostate cancer, either as long-term monotherapy, or in the initial few weeks of GnRH analog therapy.
Hormone supplementation
Progestagens
ProgestinProgestin
A progestin is a synthetic progestogen that has progestinic effects similar to progesterone. The two most common uses of progestins are for hormonal contraception , and to prevent endometrial hyperplasia from unopposed estrogen in hormone replacement therapy...
s (progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...
-like drugs) such as megestrol
Megestrol
Megestrol is a progesterone derivative with antineoplastic properties used in the treatment of advanced carcinoma of the breast and endometrium. When given in relatively high doses, Megestrol can substantially increase appetite in most individuals, even those with advanced cancer...
and medroxyprogesterone
Medroxyprogesterone
Medroxyprogesterone is a pregnane that acts as a progestin. An acylated derivative, medroxyprogesterone 17-acetate is clinically used as a drug. Compared to MPA, MP is approximately 100 fold less potent as a progestin...
have been used for the treatment of hormone-responsive, advanced breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, endometrial cancer
Endometrial cancer
Endometrial cancer refers to several types of malignancies that arise from the endometrium, or lining, of the uterus. Endometrial cancers are the most common gynecologic cancers in the United States, with over 35,000 women diagnosed each year. The incidence is on a slow rise secondary to the...
, and prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
. Progestins are also used in the treatment of endometrial hyperplasia
Endometrial hyperplasia
Endometrial hyperplasia is a condition of excessive proliferation of the cells of the endometrium, or inner lining of the uterus.Most cases of endometrial hyperplasia result from high levels of estrogens, combined with insufficient levels of the progesterone-like hormones which ordinarily...
, a precursor to endometrial adenocarcinoma. The exact mechanism of action of these hormones is unclear, and may involve both direct effect on the tumor cells (suppression of estrogen receptor levels, alteration of hormone metabolism, direct cytotoxicity) and indirect endocrine effects (suppression of adrenal androgen production and plasma estrone sulfate formation).
Androgens
The androgenAndrogen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
(testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
-like drug) Fluoxymesterone
Fluoxymesterone
Fluoxymesterone is an anabolic steroid with strong androgenic properties that has been used in the treatment of male hypogonadism, delayed puberty in males, and in the treatment of breast neoplasms in women. It is approximately 5 times as potent as methyltestosterone...
is occasionally used for the treatment of advanced breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
. The mechanism of the anticancer effects of this androgen in breast cancer are unclear, but may be analogous to those of progestins.
Estrogens
The estrogenEstrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
agonist Diethylstilbestrol
Diethylstilbestrol
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was first synthesized in 1938. Human exposure to DES occurred through diverse sources, such as dietary ingestion from supplemented cattle feed and medical treatment for certain conditions, including breast and prostate cancers...
(DES) is occasionally used to treat prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
through suppression of testosterone production. It was previously used in the treatment of breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
, but has been replaced by more effective and less toxic agents. Estrace is an estrogen which was also formerly used for anti-androgen
Androgen
Androgen, also called androgenic hormone or testoid, is the generic term for any natural or synthetic compound, usually a steroid hormone, that stimulates or controls the development and maintenance of male characteristics in vertebrates by binding to androgen receptors...
therapy of prostate cancer.
Somatostatin analogs
OctreotideOctreotide
Octreotide is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone...
is an analog of the peptide hormone somatostatin
Somatostatin
Somatostatin is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones.Somatostatin...
, which inhibits the production of the growth hormone as well as numerous peptide hormones of the gastrointestinal system, including insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...
, pancreatic polypeptide
Pancreatic polypeptide
Pancreatic polypeptide is a polypeptide secreted by PP cells in the endocrine pancreas predominantly in the head of the pancreas. It consists of 36 amino acids and has molecular weight about 4200 Da....
, gastic inhibitory polypeptide, and gastrin
Gastrin
In humans, gastrin is a peptide hormone that stimulates secretion of gastric acid by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the antrum of the stomach, duodenum, and the pancreas...
. Octreotide is used for suppression of the hormonal syndromes which accompany several pancreatic islet cell tumors, including the Zollinger-Ellison syndrome
Zollinger-Ellison syndrome
Zollinger–Ellison syndrome is a triad of gastric acid hypersecretion, severe peptic ulceration, and non-beta cell islet tumor of pancreas . In this syndrome increased levels of the hormone gastrin are produced, causing the stomach to produce excess hydrochloric acid. Often the cause is a tumor of...
of gastrinoma
Gastrinoma
A gastrinoma is a tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration in the duodenum, stomach and the small intestine. There is hypersecretion of the HCl in the duodenum which causes the ulcers...
and the chronic hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
of insulinoma
Insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin.Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is...
. It is also effective in suppression of the carcinoid syndrome
Carcinoid syndrome
Carcinoid syndrome refers to the array of symptoms that occur secondary to carcinoid tumors. The syndrome includes flushing and diarrhea, and, less frequently, heart failure and bronchoconstriction...
, caused by advanced or extra-gastrointestinal carcinoid
Carcinoid
Carcinoid is a slow-growing type of neuroendocrine tumor, originating in the cells of the neuroendocrine system.In 2000, the World Health Organization redefined "carcinoid", but this new definition has not been accepted by all practitioners. This has led to some complexity in distinguishing...
tumors. Octreotide may also be used for treatment of severe diarrhea caused by 5-fluorouracil chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
or radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
.
Non-medical hormonal interventions
In addition to the use of medication to produce tumor-suppressing endocrine alterations, destruction of endocrine organs through surgerySurgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...
or radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
are also possible. Surgical castration
Castration
Castration is any action, surgical, chemical, or otherwise, by which a male loses the functions of the testicles or a female loses the functions of the ovaries.-Humans:...
, or removal of the testes in males and ovaries in females, have been widely used in the past to treat hormone-responsive prostate cancer
Prostate cancer
Prostate cancer is a form of cancer that develops in the prostate, a gland in the male reproductive system. Most prostate cancers are slow growing; however, there are cases of aggressive prostate cancers. The cancer cells may metastasize from the prostate to other parts of the body, particularly...
and breast cancer
Breast cancer
Breast cancer is cancer originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas...
respectively. However, these invasive methods have been widely supplanted by the use of GnRH agonists, and other forms of pharmacologic castration.
There are still situations in which surgical castration may be beneficial such as in special cases for women with high risk BRCA mutation
BRCA mutation
A BRCA mutation is a mutation in either of the genes BRCA1 and BRCA2. Harmful mutations in these genes produce a hereditary breast-ovarian cancer syndrome in affected families...
s.
Hormonal immunotherapy
For more information on this topic, see ImmunotherapyImmunotherapy
Immunotherapy is a medical term defined as the "treatment of disease by inducing, enhancing, or suppressing an immune response". Immunotherapies designed to elicit or amplify an immune response are classified as activation immunotherapies. While immunotherapies that reduce or suppress are...
Hormonal stimulation of the immune system with interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
s and cytokines has been used to treat specific cancers, including renal cell carcinoma
Renal cell carcinoma
Renal cell carcinoma is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases...
and melanoma
Melanoma
Melanoma is a malignant tumor of melanocytes. Melanocytes are cells that produce the dark pigment, melanin, which is responsible for the color of skin. They predominantly occur in skin, but are also found in other parts of the body, including the bowel and the eye...
.