Molecular Pathways Molecular Pathways : Targeting Resistance in the Androgen Receptor for Therapeutic Bene fi t
Molecular Pathways Molecular Pathways : Targeting Resistance in the Androgen Receptor for Therapeutic Bene fi t
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发表时间：
2014
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通讯作者：
E. Mostaghel;S. Plymate;B. Montgomery
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文献类型：
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作者：
E. Mostaghel;S. Plymate;B. Montgomery
雄激素受体信号传导在前列腺癌的发展和进展中至关重要，这导致了深入的努力来阐明治疗干预的所有潜在拐点。这些努力揭示了新的耐药机制，并提高了已知机制可能在有效雄激素受体抑制的背景下变得更加相关的可能性。这些机制包括肿瘤对雄激素替代来源的占用、雄激素受体表达的改变、雄激素受体突变、雄激素受体截短变异体、辅因子募集到基因组中雄激素受体结合位点的改变和串扰，以及雄激素受体驱动的致癌基因融合。新的药物，如Enzalutamide、EPI-001、雄激素受体特异性肽模拟物、新型HSP 90抑制剂和PARP抑制剂，以及共同靶向雄激素受体途径的新方法，指出了更全面和持久地控制雄激素受体介导的生长的潜力。临床癌症研究; 20（4）; 1-8。2013年AACR。
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 newmechanisms of resistance and raise the possibility that knownmechanismsmay become even more relevant in the context of effective androgen receptor suppression. Thesemechanisms 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. Clin Cancer Res; 20(4); 1–8. 2013 AACR.