Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview.
Overcoming oncogene addiction in breast and prostate cancers: a comparative mechanistic overview.
复制标题
克服乳腺癌和前列腺癌中的癌基因成瘾：比较机制综述。
DOI：
10.1530/erc-20-0272
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发表时间：
2021-03
影响因子：
3.9
通讯作者：
Raj GV
中科院分区：
文献类型：
--
作者：
Blatt EB;Kopplin N;Kumar S;Mu P;Conzen SD;Raj GV
前列腺癌（PCa）和乳腺癌（BCa）都是激素依赖性癌症，分别需要雄激素受体（AR）和雌激素受体（ER, ESR1）来生长和增殖。针对这些核受体（NRs）的内分泌治疗为转移性患者提供了显著的临床益处。然而，这些治疗策略很少能治愈，而且治疗耐药性普遍存在。由于绝大多数耐药PCa和BCa仍然依赖于其主要NR驱动因子活性的增强，耐药的常见机制包括通过受体的过表达、突变或选择性剪接、共调节因子改变和增加分泌激素合成来增强NR信号。此外，一个重要的内分泌治疗耐药肿瘤亚群变得独立于其原始NR，并转向替代NR或转录驱动因子。虽然这些激素依赖性癌症通常采用相似的内分泌治疗抵抗机制，但已经观察到两种肿瘤类型之间存在明显差异。在这篇综述中，我们比较和对比了抗雄激素和抗雌激素抵抗的最常见机制，并提供针对晚期前列腺癌和BCa的潜在治疗策略。
Prostate cancer (PCa) and breast cancer (BCa) are both hormone-dependent cancers that require the androgen receptor (AR) and estrogen receptor (ER, ESR1) for growth and proliferation, respectively. Endocrine therapies that target these nuclear receptors (NRs) provide significant clinical benefit for metastatic patients. However, these therapeutic strategies are seldom curative and therapy resistance is prevalent. Because the vast majority of therapy-resistant PCa and BCa remain dependent on the augmented activity of their primary NR driver, common mechanisms of resistance involve enhanced NR signaling through overexpression, mutation, or alternative splicing of the receptor, coregulator alterations, and increased intracrine hormonal synthesis. In addition, a significant subset of endocrine therapy-resistant tumors become independent of their primary NR and switch to alternative NR or transcriptional drivers. While these hormone-dependent cancers generally employ similar mechanisms of endocrine therapy resistance, distinct differences between the two tumor types have been observed. In this review, we compare and contrast the most frequent mechanisms of antiandrogen and antiestrogen resistance, and provide potential therapeutic strategies for targeting both advanced PCa and BCa.