The potential role of estrogen receptors and the SRC family as targets for the treatment of breast cancer.
BACKGROUND
Breast cancer has a number of subtypes, the main ones are estrogen-receptor (ER)-positive, luminal type A and B. Treatment selection, with respect to hormonal therapy, is based upon ER expression. Whilst for ER-positive cancers, endocrine therapy is highly successful in the adjuvant setting, a significant proportion of cancers exhibit hormone resistance, often associated with altered growth factor receptor or ER signalling. Modulation of steroid receptor function by receptor co-activators or repressors is a potential mechanism of resistance. The p160 or SRC proto-oncogene family of co-activators are important in breast cancer response to endocrine therapy and can act as a paradigm of co-activator function.


OBJECTIVE
This review focuses on the role of ER and ER co-activators in breast cancer and current approaches to targeting SRC co-factors for treatment of hormone-receptor-positive breast cancer.


CONCLUSIONS
There is a drive to selectively apply aromatase inhibitors on the basis of either risk or biological evidence of resistance to tamoxifen treatment. Both strategies may yield improved treatment to benefit ratios.
Spears
Melanie
M
University of Edinburgh, Edinburgh Cancer Research Centre, Crewe Road South, Edinburgh EH42XR, UK.
Bartlett
John
J
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D020847:Estrogen Receptor Modulators / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000187:drug effects* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D000090063:Proto-Oncogene Mas; D015398:Signal Transduction; D019061:src-Family Kinases / Q000187:drug effects* / Q000378:metabolism
D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019061:src-Family Kinases