Department of Oncology, University of Turin, at Division of Medical Oncology, San Luigi Gonzaga Hospital, Regione Gonzole 10, 10043, Orbassano, Turin, Italy.
Medical Oncology, Cardinal Massaia Hospital, Corso Dante Alighieri 202, 14100, Asti, Italy.
Crit Rev Oncol Hematol. 2021 Jan;157:103185. doi: 10.1016/j.critrevonc.2020.103185. Epub 2020 Nov 27.
In last years several improvements have been made in the management of prostate cancer (PCa). Androgen receptor (AR) is considered the main driver in PCa growth and progression and most drugs are directed against AR pathway. Once PCa spreads outside the prostate, androgen deprivation therapy (ADT) represents the cornerstone of treatment in hormone-sensitive prostate cancer (HSPC). Unfortunately, the response is only transient and most patients eventually develop castration-resistant prostate cancer (CRPC). Most resistance mechanisms depend on maintenance of AR signalling in castration environment. Recent discoveries of multiple growth-promoting and survival pathways in PCa suggest the importance of alternative mechanisms involved in disease progression, such as DNA damage response pathway, PTEN/PI3K/AKT/mTOR pathway, cell cycle pathway, WNT pathway, TMPRSS2/ETS fusion, neuroendocrine pattern and immune system response. In this review, we discuss the interplay between AR signaling and other molecular pathways involved in PCa pathogenesis and their therapeutic implication in advanced disease.
近年来，前列腺癌 (PCa) 的治疗取得了多项进展。雄激素受体 (AR) 被认为是 PCa 生长和进展的主要驱动因素，大多数药物都针对 AR 通路。一旦 PCa 扩散到前列腺之外，雄激素剥夺疗法 (ADT) 就成为激素敏感型前列腺癌 (HSPC) 的治疗基石。不幸的是，这种反应只是暂时的，大多数患者最终会发展为去势抵抗性前列腺癌 (CRPC)。大多数耐药机制依赖于在去势环境中维持 AR 信号。最近在 PCa 中发现的多种促进生长和存活的途径表明，参与疾病进展的替代机制的重要性，如 DNA 损伤反应途径、PTEN/PI3K/AKT/mTOR 途径、细胞周期途径、WNT 途径、TMPRSS2/ETS 融合、神经内分泌模式和免疫系统反应。在这篇综述中，我们讨论了 AR 信号与其他参与 PCa 发病机制的分子途径之间的相互作用及其在晚期疾病中的治疗意义。
