靶向PI3K/AKT通路在前列腺癌症中的作用：PTEN缺乏和生物标志物引导的治疗

摘要(中文译文)

肿瘤抑制基因的缺失是晚期前列腺癌常见的分子特征，并与PI3K/AKT信号通路的激活相关，该通路调控细胞生长与存活。尽管转移性去势敏感性前列腺癌（mCSPC）的治疗已取得重大进展，但PTEN缺陷型肿瘤患者仍属于侵袭性亚组，临床结局较差且靶向治疗选择有限。Capivasertib是一种选择性口服AKT抑制剂，旨在抑制PI3K通路激活所介导的下游信号传导。我们重点介绍近期III期CAPItello-281试验（NCT04493853）的结果，该研究表明，在醋酸阿比特龙联合雄激素剥夺治疗（ADT）的基础上加用capivasertib可显著改善PTEN缺陷型mCSPC患者的影像学无进展生存期，并促使该方案获得FDA批准。capivasertib组值得关注的不良事件包括高血糖、腹泻和皮疹。CAPItello-281填补了PTEN缺陷型mCSPC领域一项重要的未满足需求，提示AKT抑制可作为预后不良亚群潜在的新型靶向治疗策略。

Abstract

Loss of the tumor suppressor gene is a common molecular feature in advanced prostate cancer and is associated with activation of the PI3K/AKT signaling pathway, which controls cell growth and survival. Despite major advances in the treatment of metastatic castration-sensitive prostate cancer (mCSPC), patients with PTEN-deficient tumors represent an aggressive subgroup with poorer clinical outcomes and limited targeted therapeutic options. Capivasertib is a selective oral AKT inhibitor designed to suppress downstream signaling from PI3K pathway activation. We highlight the recent results from the Phase III CAPItello-281 trial (NCT04493853) demonstrating that the addition of capivasertib to abiraterone acetate and androgen deprivation therapy (ADT) significantly improved radiographic progression-free survival in patients with -deficient mCSPC, leading to the FDA-approval of this regimen. Notable adverse events in the cabavisertib arm included hyperglycemia, diarrhea, and rash. CAPItello-281 addresses a significant unmet need for -deficient mCSPC, suggesting AKT inhibition as a potential new targeted treatment strategy for a sub-population with poor prognosis.

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