Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance.
Non-Coding RNAs Set a New Phenotypic Frontier in Prostate Cancer Metastasis and Resistance.
复制标题
DOI：
10.3390/ijms22042100
复制
发表时间：
2021-02-20
影响因子：
5.6
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Altschuler J;Stockert JA;Kyprianou N
前列腺癌（PCa）死亡率仍然是一个重大的公共卫生问题，因为晚期疾病由于对标准和新型治疗干预措施的耐药性的发展而具有较差的生存能力。治疗抗性是一个多方面的问题，涉及许多生物学机制的相互作用，包括遗传、信号传导和表型改变，以及支持肿瘤生长、侵袭和转移的肿瘤微环境的贡献。雄激素受体（AR）是前列腺细胞生长、反应和维持的主要调节因子，并且是设计用于抑制AR与雄激素（其天然配体）相互作用的大多数标准PCa疗法的靶标。因此，AR仍然是转移性去势抵抗性前列腺癌（mCRPC）患者治疗反应的主要驱动因素。虽然雄激素剥夺治疗（ADT）联合微管靶向紫杉烷化疗可为mCRPC患者提供生存获益，但治疗耐药性总是会发展，导致致命性疾病。了解耐药性的潜在机制对于改善治疗结果以及开发具有预测价值的生物标志物特征至关重要。上皮细胞向间充质细胞转化（EMT）和间充质细胞向上皮细胞转化（MET）之间的相互转化指导前列腺肿瘤的治疗反应，并提供了克服治疗耐药性的新型靶向平台。microRNA（miRNA）和长链非编码RNA（lncRNA）介导的机制都与前列腺癌的表观遗传变化有关。本综述讨论了目前的循证知识的作用，表型转换和新的分子决定因素（非编码RNA）的贡献者出现的治疗耐药和转移，其综合预测价值前列腺癌进展到晚期疾病。
Prostate cancer (PCa) mortality remains a significant public health problem, as advanced disease has poor survivability due to the development of resistance in response to both standard and novel therapeutic interventions. Therapeutic resistance is a multifaceted problem involving the interplay of a number of biological mechanisms including genetic, signaling, and phenotypic alterations, compounded by the contributions of a tumor microenvironment that supports tumor growth, invasiveness, and metastasis. The androgen receptor (AR) is a primary regulator of prostate cell growth, response and maintenance, and the target of most standard PCa therapies designed to inhibit AR from interacting with androgens, its native ligands. As such, AR remains the main driver of therapeutic response in patients with metastatic castration-resistant prostate cancer (mCRPC). While androgen deprivation therapy (ADT), in combination with microtubule-targeting taxane chemotherapy, offers survival benefits in patients with mCRPC, therapeutic resistance invariably develops, leading to lethal disease. Understanding the mechanisms underlying resistance is critical to improving therapeutic outcomes and also to the development of biomarker signatures of predictive value. The interconversions between epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) navigate the prostate tumor therapeutic response, and provide a novel targeting platform in overcoming therapeutic resistance. Both microRNA (miRNA)- and long non-coding RNA (lncRNA)-mediated mechanisms have been associated with epigenetic changes in prostate cancer. This review discusses the current evidence-based knowledge of the role of the phenotypic transitions and novel molecular determinants (non-coding RNAs) as contributors to the emergence of therapeutic resistance and metastasis and their integrated predictive value in prostate cancer progression to advanced disease.
登录
查看更多内容
DOI：
10.1038/nrc.2017.99
发表时间：
2018-01
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Anastasiadou E;Jacob LS;Slack FJ
通讯作者：
Slack FJ
影响因子：
82.9
作者：
Beltran H;Prandi D;Mosquera JM;Benelli M;Puca L;Cyrta J;Marotz C;Giannopoulou E;Chakravarthi BV;Varambally S;Tomlins SA;Nanus DM;Tagawa ST;Van Allen EM;Elemento O;Sboner A;Garraway LA;Rubin MA;Demichelis F
通讯作者：
Demichelis F
影响因子：
9
作者：
Ali A;Zhang P;Liangfang Y;Wenshe S;Wang H;Lin X;Dai Y;Feng XH;Moses R;Wang D;Li X;Xiao J
通讯作者：
Xiao J
影响因子：
4.8
作者：
Bohl, CE;Miller, DD;Dalton, JT
通讯作者：
Dalton, JT
影响因子：
21.3
作者：
Batlle, E;Sancho, E;de Herreros, AG
通讯作者：
de Herreros, AG