Laudato Sara, Aparicio Ana, Giancotti Filippo G
Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; David H. Koch Center for Applied Research of Genitourinary Cancers, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Trends Cancer. 2019 Jul;5(7):440-455. doi: 10.1016/j.trecan.2019.05.008. Epub 2019 Jun 29.
In spite of an initial clinical response to androgen deprivation therapy (ADT), the majority of prostate cancer patients eventually develop castration-resistant prostate cancer (CRPC). Recent studies have highlighted the role of epithelial plasticity, including transdifferentiation and epithelial-to-mesenchymal transition (EMT), in the development of AR pathway-negative CRPC, a form of the disease that has increased in incidence after the introduction of potent AR inhibitors. In this review, we will discuss the switches between different cell fates that occur in response to AR blockade or acquisition of specific oncogenic mutations, such as those in TP53 and RB1, during the evolution to CRPC. We highlight the urgent need to dissect the mechanistic underpinnings of these transitions and identify novel vulnerabilities that can be targeted therapeutically.
尽管雄激素剥夺疗法（ADT）最初有临床反应，但大多数前列腺癌患者最终会发展为去势抵抗性前列腺癌（CRPC）。最近的研究强调了上皮可塑性，包括转分化和上皮-间质转化（EMT），在AR通路阴性CRPC发生发展中的作用，这种疾病在强效AR抑制剂引入后发病率有所增加。在这篇综述中，我们将讨论在向CRPC演变过程中，因AR阻断或获得特定致癌突变（如TP53和RB1中的突变）而发生的不同细胞命运之间的转换。我们强调迫切需要剖析这些转变的机制基础，并确定可作为治疗靶点的新弱点。
