The SERM Saga, Something from Nothing: American Cancer Society/SSO Basic Science Lecture.
Ann Surg Oncol
; 26(7): 1981-1990, 2019 Jul.
Article
en En
| MEDLINE
| ID: mdl-30911948
ABSTRACT
BACKGROUND:
The discovery of nonsteroidal antiestrogens created a new group of medicines looking for an application; however, at the time, cytotoxic chemotherapy was the modality of choice to treat all cancers. Antiestrogens were orphan drugs until 1971, with the passing of the National Cancer Act. This enabled laboratory innovations to aid patient care.METHODS:
This article traces the strategic application of tamoxifen to treat breast cancer by targeting the estrogen receptor (ER), deploying long-term adjuvant tamoxifen therapy, and becoming the first chemopreventive for any cancer. Laboratory discoveries from the University of Wisconsin Comprehensive Cancer Center (UWCCC) are described that address a broad range of biological issues with tamoxifen. These translated to improvements in clinical care.RESULTS:
Tamoxifen was studied extensively at UWCCC in the 1980s for the development of acquired resistance to long-term therapy. Additionally, the long-term metabolism of tamoxifen and regulation of growth factors were also studied. A concern with tamoxifen use for chemoprevention was that an antiestrogen would increase bone loss and atherosclerosis. Laboratory studies with tamoxifen and keoxifene (subsequently named raloxifene) demonstrated that 'nonsteroidal antiestrogens' maintained bone density, and this translated into successful clinical trials with tamoxifen at UWCCC. However, tamoxifen also increased endometrial cancer growth; this discovery in the laboratory translated into changes in clinical care. Selective estrogen receptor modulators (SERMs) were born at UWCCC.CONCLUSIONS:
There are now five US FDA-approved SERMs, all with discovery origins at UWCCC. Women's health was revolutionized as SERMs have the ability to treat multiple diseases by switching target sites around a woman's body on or off.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Receptores de Estrógenos
/
Moduladores Selectivos de los Receptores de Estrógeno
Límite:
Female
/
Humans
Idioma:
En
Revista:
Ann Surg Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos