Ferroptosis is a distinct form of regulated cell death that is predominantly driven by the build-up of intracellular iron and lipid peroxides. Ferroptosis suppression is widely accepted to contribute to the pathogenesis of several tumours including prostate cancer. Results from some studies reported that prostate cancer cells can be highly susceptible to ferroptosis inducers, providing potential for an interesting new avenue of therapeutic intervention for advanced prostate cancer. In this Perspective, we describe novel molecular underpinnings and metabolic drivers of ferroptosis, analyse the functions and mechanisms of ferroptosis in tumours, and highlight prostate cancer-specific susceptibilities to ferroptosis by connecting ferroptosis pathways to the distinctive metabolic reprogramming of prostate cancer cells. Leveraging these novel mechanistic insights could provide innovative therapeutic opportunities in which ferroptosis induction augments the efficacy of currently available prostate cancer treatment regimens, pending the elimination of major bottlenecks for the clinical translation of these treatment combinations, such as the development of clinical-grade inhibitors of the anti-ferroptotic enzymes as well as non-invasive biomarkers of ferroptosis. These biomarkers could be exploited for diagnostic imaging and treatment decision-making.

铁死亡是一种独特的受调节细胞死亡形式，主要由细胞内铁和脂质过氧化物的积累驱动。铁死亡抑制被广泛认为有助于包括前列腺癌在内的多种肿瘤的发病机制。一些研究结果表明，前列腺癌细胞对铁死亡诱导剂高度敏感，这为晚期前列腺癌的治疗干预提供了一种有趣的新途径。在这篇文章中，我们描述了铁死亡的新分子基础和代谢驱动因素，分析了肿瘤中铁死亡的功能和机制，并通过将铁死亡途径与前列腺癌细胞独特的代谢重编程联系起来，强调了前列腺癌对铁死亡的特异性易感性。利用这些新颖的机制见解可以提供创新的治疗机会，其中铁死亡诱导增强了目前可用的前列腺癌治疗方案的功效，等待消除这些治疗组合临床转化的主要瓶颈，例如开发临床级抑制剂抗铁死亡酶以及铁死亡的非侵入性生物标志物。这些生物标志物可用于诊断成像和治疗决策。