Selectively targeting estrogen receptors for cancer treatment.
Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ERα and ERβ, which mediate proliferation and differentiation of cells. For decades, ERα mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most notably with the selective estrogen receptor modulator (SERM) tamoxifen. Selectively targeting ERs occurs at two levels: tissue selectivity and receptor subtype selectivity. SERMs have been developed with emphasis on tissue selectivity to target ER signaling for breast cancer treatment. Additionally, new approaches to selectively target the action of ERα going beyond ligand-dependent activity are under current investigation. As evidence of the anti-proliferative role of ERβ accumulates, selectively targeting ERβ is an attractive approach for designing new cancer therapies with the emphasis shifted to designing ligands with subtype selectivity. This review will present the mechanistic and structural features of ERs that determine tissue and subtype selectivity with an emphasis on current approaches to selectively target ERα and ERβ for cancer treatment.
Shanle
Erin K
EK
McArdle Laboratory for Cancer Research, University of Wisconsin, 1400 University Avenue, Madison, WI 53706, USA.
Xu
Wei
W
D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008968:Molecular Conformation; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use*; D015398:Signal Transduction; D013329:Structure-Activity Relationship
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D020845:Selective Estrogen Receptor Modulators