文章：

PI3Kδ作为侵袭性前列腺癌的新型治疗靶点

PI3Kδ as a Novel Therapeutic Target for Aggressive Prostate Cancer

原文发布日期：9 May 2025

DOI: 10.3390/cancers17101610

类型: Article

开放获取: 是

英文摘要：

Phosphoinositide 3-kinases (PI3Ks) signaling represents an important pathway regulating cell proliferation, survival, invasion, migration, and metabolism. Notably, PI3K/AKT/mTOR signaling is frequently dysregulated in the majority of malignancies. Among the class IA PI3Ks (PI3Kα/β/δ), emerging evidence has implicated that PI3Kδ is not only overexpressed in leukocytes but also in solid tumors, including prostate cancer. The critical role of PI3Kδ in tumorigenesis and in the creation of a suppressive tumor microenvironment, along with the recent finding of PI3Kδ splice isoforms in promoting tumor aggressiveness and resistance, further demonstrates the potential of developing novel PI3Kδ-targeted cancer therapies. In this review, we comprehensively describe the functional mechanisms underlying the PI3Kδ-driven tumor progression and immune regulation in prostate cancer diseases. Furthermore, the recent preclinical and clinical studies on the development of PI3Kδ-/PI3K-targeted inhibitors as single agents and in combination therapies (with chemotherapy, radiation, hormone therapy, or immunotherapy) are summarized. Finally, we discuss the potential novel therapies for improving the treatment efficacies, as well as the current limitations and challenges of PI3Kδ-based therapies for prostate cancer.

摘要翻译： 

磷酸肌醇3-激酶（PI3Ks）信号通路是调控细胞增殖、存活、侵袭、迁移及代谢的重要途径。值得注意的是，PI3K/AKT/mTOR信号通路在多数恶性肿瘤中常出现失调。在IA类PI3Ks（PI3Kα/β/δ）中，最新证据表明PI3Kδ不仅在白细胞中过度表达，在前列腺癌等实体肿瘤中也存在异常高表达。PI3Kδ在肿瘤发生及抑制性肿瘤微环境形成中的关键作用，加之近期发现其剪接异构体能促进肿瘤侵袭性与耐药性，进一步证实了开发新型PI3Kδ靶向癌症疗法的潜力。本综述系统阐述了PI3Kδ驱动前列腺癌进展及免疫调控的功能机制，并总结了近期针对PI3Kδ/PI3K靶向抑制剂作为单药或联合疗法（与化疗、放疗、激素疗法或免疫疗法联用）的临床前及临床研究进展。最后，我们探讨了提升治疗效果的新型疗法潜力，以及当前基于PI3Kδ的前列腺癌疗法存在的局限性与挑战。

原文链接：

PI3Kδ as a Novel Therapeutic Target for Aggressive Prostate Cancer