Masonic Cancer Center, University of Minnesota-Twin Cities, Minneapolis, MN, USA.
Department of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Expert Rev Anticancer Ther. 2024 Nov;24(11):1085-1100. doi: 10.1080/14737140.2024.2405103. Epub 2024 Sep 20.
Prostate cancer continues to be a major cause of morbidity and mortality for men worldwide. Enzalutamide, a second-generation non-steroidal antiandrogen that blocks androgen receptor (AR) transcriptional activity, is a treatment for biochemically recurrent, metastatic, castration-sensitive, and castration-resistant tumors. Unfortunately, most patients ultimately develop resistance to enzalutamide, making long-term treatment with this agent challenging.
We performed a literature search of PubMed without date restrictions to investigate the literature surrounding enzalutamide and discuss the current uses of enzalutamide, proposed mechanisms driving resistance, and summarize current efforts to mitigate this resistance.
Enzalutamide is an effective prostate cancer therapy that is currently used in biochemically recurrent and metastatic disease and for both castration-sensitive and castration-resistant tumors. Unfortunately, resistance to enzalutamide occurs in each of these scenarios. In the clinical setting, enzalutamide-resistant tumors are either AR-driven or AR-indifferent. AR-dependent resistance mechanisms include genomic or epigenomic events that result in enhanced AR signaling. Tumors that do not require AR signaling instead may depend on alternative oncogenic pathways. There are numerous strategies to mitigate enzalutamide resistance, including concurrent use of PARP inhibitors or immune therapies. Additional work is required to uncover novel approaches to treat patients in the enzalutamide-resistant setting.
前列腺癌仍然是全球男性发病和死亡的主要原因。恩扎鲁胺是一种第二代非甾体抗雄激素药物，可阻断雄激素受体（AR）转录活性，用于治疗生化复发、转移性、去势敏感和去势抵抗性肿瘤。不幸的是，大多数患者最终会对恩扎鲁胺产生耐药性，这使得长期使用该药物具有挑战性。
我们在 PubMed 上进行了无时间限制的文献检索，以调查有关恩扎鲁胺的文献，并讨论恩扎鲁胺的当前用途、耐药的潜在机制以及目前缓解耐药性的努力。
恩扎鲁胺是一种有效的前列腺癌治疗药物，目前用于生化复发和转移性疾病以及去势敏感和去势抵抗性肿瘤。不幸的是，在这些情况下都会发生对恩扎鲁胺的耐药性。在临床环境中，恩扎鲁胺耐药的肿瘤要么是 AR 驱动的，要么是 AR 不依赖的。AR 依赖性耐药机制包括导致 AR 信号增强的基因组或表观基因组事件。不需要 AR 信号的肿瘤可能依赖于替代致癌途径。有许多策略可以减轻恩扎鲁胺的耐药性，包括同时使用 PARP 抑制剂或免疫疗法。需要进一步的工作来发现治疗恩扎鲁胺耐药患者的新方法。
