The role of epithelial plasticity in prostate cancer dissemination and treatment resistance.
The role of epithelial plasticity in prostate cancer dissemination and treatment resistance.
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DOI：
10.1007/s10555-013-9483-z
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发表时间：
2014-09
影响因子：
9.2
通讯作者：
Armstrong, Andrew J.
中科院分区：
文献类型：
--
作者：
Bitting, Rhonda L.;Schaeffer, Daneen;Somarelli, Jason A.;Garcia-Blanco, Mariano A.;Armstrong, Andrew J.
关键词：
在美国，每年有近 30,000 名男性死于前列腺癌，几乎全部死于转移性传播。尽管最近在激素、免疫、骨靶向和细胞毒性化疗方面取得了进展，但对于患有转移性疾病的男性来说，治疗耐药性和进一步传播是不可避免的。新数据表明，上皮可塑性现象（包括可逆间充质转变和干性特征的获得）可能是这种致命的传播和治疗抵抗生物学的基础。从前列腺癌的临床前模型和人类转移性前列腺癌的生物标志物研究中了解这种细胞可塑性的分子基础，为新的治疗方法提供了线索，这些方法可能会随着时间的推移延迟或预防转移性疾病和致死率。这篇综述将讨论这个快速变化领域中上皮可塑性的临床前和临床证据，并将其与前列腺癌的临床表型和耐药性联系起来，同时提出新的治疗方法。
Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches.
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