借力推动前列腺癌 CAR-T 细胞治疗进展
Piggybacking toward Progress for CAR T-Cell Therapy in Prostate Cancer.
P-PSMA-101 是一款首创的、富集干细胞记忆 T 细胞的、靶向前列腺特异性膜抗原(PSMA)的嵌合抗原受体(CAR)T 疗法。
英文原题:Evolving Treatments and Resistance Mechanisms in Prostate Cancer Therapeutics.
前列腺癌仍然是男性癌症相关发病率和死亡率的主要原因,其根本驱动因素是雄激素受体(AR)信号轴的功能获得性改变。
前列腺癌仍然是男性癌症相关发病率和死亡率的主要原因,其根本驱动因素是雄激素受体(AR)信号轴的功能获得性改变。尽管从雄激素剥夺治疗到下一代抗雄激素药物等重大治疗进展已显著改善临床结局,但疾病进展和治疗耐药的出现仍构成重大的临床挑战。本综述全面概述了前列腺癌的历史和当代治疗策略,特别强调治疗耐药和疾病演变的分子机制。为支持本综述所呈现的论述,我们纳入了选定的计算机分析,例如抗雄激素与AR相互作用的分子对接研究,旨在补充已发表的结构和功能研究,并为所综述的文献提供机制背景。此外,我们重点介绍了新兴和不断演变的治疗模式,包括过继细胞治疗、基于纳米医学的药物递送、聚(ADP核糖)聚合酶(PARP)抑制、蛋白水解靶向嵌合体(PROTAC)技术以及基于RNA的方法,并强调其转化潜力和当前局限性。通过将现有文献与有针对性的计算机见解相结合,本视角提出了克服耐药和推进前列腺癌精准治疗的前瞻性观点。
Prostate cancer remains a leading cause of cancer-related morbidity and mortality among men, fundamentally driven by gain-of-function alterations in the androgen receptor (AR) signaling axis. Although major therapeutic advances from androgen deprivation therapy to next-generation antiandrogens have significantly improved clinical outcomes, disease progression and the emergence of therapeutic resistance continue to pose substantial clinical challenges. This review provides a comprehensive overview of historical and contemporary treatment strategies in prostate cancer with particular emphasis on the molecular mechanisms underlying therapeutic resistance and disease evolution. To support the narrative presented in this review, we incorporate selected in silico analyses, such as molecular docking studies of antiandrogen AR interactions, which are intended to complement published structural and functional studies and provide a mechanistic context to the reviewed literature. In addition, we highlight emerging and evolving therapeutic modalities, including adoptive cell therapy, nanomedicine-based drug delivery, poly-(ADP ribose) polymerase (PARP) inhibition, proteolysis-targeting chimera (PROTAC) technologies, and RNA-based approaches, with emphasis on their translational potential and current limitations. By integrating the existing literature with targeted in silico insights, this perspective presents a forward-looking perspective on overcoming resistance and advancing precision therapeutics in prostate cancer.
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