title: Molecular pathways: targeting resistance in the androgen receptor for therapeutic benefit.
abstract: Androgen receptor signaling is critical in the development and progression of prostate cancer, leading to intensive efforts to elucidate all potential points of inflection for therapeutic intervention. These efforts have revealed new mechanisms of resistance and raise the possibility that known mechanisms may become even more relevant in the context of effective androgen receptor suppression. These mechanisms include tumoral appropriation of alternative androgen sources, alterations in androgen receptor expression, androgen receptor mutations, truncated androgen receptor variants, alterations and cross-talk in recruitment of cofactors to androgen receptor binding sites in the genome, and androgen receptor-driven oncogenic gene fusions. New agents such as enzalutamide, EPI-001, androgen receptor-specific peptidomimetics, novel HSP90 inhibitors, and PARP inhibitors, as well as new approaches to cotargeting the androgen receptor pathway, point to the potential for more complete and durable control of androgen receptor-mediated growth.
authors.affiliation: Authors' Affiliations: Division of Clinical Research, Fred Hutchinson Cancer Research Center; and Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Elahe A
authors.initials: EA
authors.lastname: Mostaghel
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Plymate
authors.forename: Bruce
authors.initials: B
authors.lastname: Montgomery
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009154:Mutation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D011944:Receptors, Androgen