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Abstract：
Prostate cancer (PC) is a common malignancy among elderly men, characterized by great heterogeneity in its clinical course, ranging from an indolent to a highly aggressive disease. The aggressive variant of prostate cancer (AVPC) clinically shows an atypical pattern of disease progression, similar to that of small cell PC (SCPC), and also shares the chemo-responsiveness of SCPC. The term AVPC does not describe a specific histologic subtype of PC but rather the group of tumors that, irrespective of morphology, show an aggressive clinical course, dictated by androgen receptor (AR) indifference. AR indifference represents an adaptive response to androgen deprivation therapy (ADT), driven by epithelial plasticity, an inherent ability of tumor cells to adapt to their environment by changing their phenotypic characteristics in a bi-directional way. The molecular profile of AVPC entails combined alterations in the tumor suppressor genes retinoblastoma protein 1 (RB1), tumor protein 53 (TP53), and phosphatase and tensin homolog (PTEN). The understanding of the biologic heterogeneity of castration-resistant PC (CRPC) and the need to identify the subset of patients that would potentially benefit from specific therapies necessitate the development of prognostic and predictive biomarkers. This review aims to discuss the possible pathophysiologic mechanisms of AVPC development and the potential use of emerging tissue-based biomarkers in clinical practice.
摘要：
前列腺癌（PC）是老年男性常见的恶性肿瘤，其临床过程具有很大的异质性，从惰性到高度侵袭性的疾病。前列腺癌的侵袭性变体（AVPC）在临床上显示出疾病进展的非典型模式，类似于小型蜂窝PC(SPC)，并且还共享SCPC的化学响应性。术语AVPC不描述PC的特定组织学亚型，而是描述肿瘤组，无论形态如何，表现出积极的临床过程，由雄激素受体（AR）冷漠决定。AR冷漠代表对雄激素剥夺治疗（ADT）的适应性反应，由上皮可塑性驱动，肿瘤细胞通过双向改变其表型特征来适应环境的固有能力。AVPC的分子谱需要肿瘤抑制基因视网膜母细胞瘤蛋白1（RB1）的联合改变，肿瘤蛋白53（TP53），和磷酸酶和张力蛋白同源物(PTEN)。对去势抗性PC（CRPC）的生物学异质性的理解以及确定可能从特定疗法中受益的患者子集的需要需要开发预后和预测性生物标志物。这篇综述旨在讨论AVPC发展的可能病理生理机制以及新兴的基于组织的生物标志物在临床实践中的潜在用途。
