Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity.
Phenotypic Plasticity, Bet-Hedging, and Androgen Independence in Prostate Cancer: Role of Non-Genetic Heterogeneity.
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DOI：
10.3389/fonc.2018.00050
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发表时间：
2018
影响因子：
4.7
通讯作者：
Levine H
中科院分区：
文献类型：
--
作者：
Jolly MK;Kulkarni P;Weninger K;Orban J;Levine H
众所周知，基因突变会导致耐药性并导致肿瘤复发。在这里，我们关注替代机制——那些没有突变的机制，例如表型可塑性和细胞间的随机变异，它们也可以通过产生耐药的持久性来逃避药物攻击。这种持久性现象已在细菌中得到了充分研究，最近在癌症中也引起了人们的关注。我们将前列腺癌（PCa）中的细菌持久性和对雄激素剥夺疗法的耐药性进行了比较，前列腺癌是转移性疾病的主要标准治疗方法。我们说明了表型可塑性和随后可能由蛋白质构象动力学驱动的与突变无关或非遗传异质性如何随机引起前列腺癌的雄激素独立性，并建议在设计用于治疗和管理前列腺癌的治疗剂量策略时应考虑动态表型可塑性。
It is well known that genetic mutations can drive drug resistance and lead to tumor relapse. Here, we focus on alternate mechanisms—those without mutations, such as phenotypic plasticity and stochastic cell-to-cell variability that can also evade drug attacks by giving rise to drug-tolerant persisters. The phenomenon of persistence has been well-studied in bacteria and has also recently garnered attention in cancer. We draw a parallel between bacterial persistence and resistance against androgen deprivation therapy in prostate cancer (PCa), the primary standard care for metastatic disease. We illustrate how phenotypic plasticity and consequent mutation-independent or non-genetic heterogeneity possibly driven by protein conformational dynamics can stochastically give rise to androgen independence in PCa, and suggest that dynamic phenotypic plasticity should be considered in devising therapeutic dosing strategies designed to treat and manage PCa.
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
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Abranches, Elsa;Guedes, Ana M. V.;Henrique, Domingos
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