Targeting molecular resistance in castration-resistant prostate cancer.
Targeting molecular resistance in castration-resistant prostate cancer.
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DOI：
10.1186/s12916-015-0457-6
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发表时间：
2015-09-01
期刊：
影响因子：
9.3
通讯作者：
Evans CP
中科院分区：
文献类型：
--
作者：
Chandrasekar T;Yang JC;Gao AC;Evans CP
多种耐药机制参与了激素敏感型前列腺癌向去势耐药前列腺癌(CRPC)的不可避免进展。目前批准的CRPC治疗方法包括全身化疗(多西紫杉醇和卡巴紫杉醇)和针对导致CRPC的耐药途径的药物，包括苯扎鲁胺和阿比特龙。虽然有显著的生存益处，但对这些疗法的原发和继发耐药发展迅速。多达三分之一的患者对苯扎鲁胺和阿比特龙有初步耐药性；其余患者最终在治疗方面取得进展。了解耐药导致进展的机制以及确定新的靶向途径仍然是当前前列腺癌研究的重点。我们回顾了目前对目前批准的治疗耐药机制的现有知识，辅助治疗的发展，以及针对治疗目的识别新的通路。
Multiple mechanisms of resistance contribute to the inevitable progression of hormone-sensitive prostate cancer to castration-resistant prostate cancer (CRPC). Currently approved therapies for CRPC include systemic chemotherapy (docetaxel and cabazitaxel) and agents targeting the resistance pathways leading to CRPC, including enzalutamide and abiraterone. While there is significant survival benefit, primary and secondary resistance to these therapies develops rapidly. Up to one-third of patients have primary resistance to enzalutamide and abiraterone; the remaining patients eventually progress on treatment. Understanding the mechanisms of resistance resulting in progression as well as identifying new targetable pathways remains the focus of current prostate cancer research. We review current knowledge of mechanisms of resistance to the currently approved treatments, development of adjunctive therapies, and identification of new pathways being targeted for therapeutic purposes.