前列腺癌是男性中最常见的恶性肿瘤之一，约有8分之1的男性在其余生期内被诊断出患有该疾病。寻找新的治疗干预方法的紧急性与去势抵抗前列腺癌的治疗耐受性和死亡率相关。不附着在细胞外基质（ECM）上的正常上皮或内皮细胞所发生的细胞凋亡现象称为解离性凋亡。失去与 ECM 的连接的肿瘤细胞可以通过凋亡而死亡，或通过解离性凋亡耐受性而幸存并逃避到远处器官进行转移。本综述讨论了我们对前列腺癌中解离性凋亡信号效应物的最新进展及将这些机制洞察转化成治疗益处以减少致命疾病结果（通过克服解离性凋亡耐受性）的方法。前列腺肿瘤微环境是一个高度动态的景观，其中雄激素信号、细胞系谱变化、上皮间质转化（EMT）、细胞外基质相互作用、肌动蛋白细胞骨架重塑以及代谢变化之间的平衡，赋予了解离性凋亡耐受性和转移扩散的特性。因此，这些机制也提供了独特的分子治疗标志，利用这些标志可以为前列腺肿瘤诱导解离性凋亡提供高度相关的译码意义。版权所有©Nepali 和 Kyprianou。

Prostate cancer is one of the most common malignancies in males wherein 1 in 8 men are diagnosed with this disease in their lifetime. The urgency to find novel therapeutic interventions is associated with high treatment resistance and mortality rates associated with castration-resistant prostate cancer. Anoikis is an apoptotic phenomenon for normal epithelial or endothelial cells that have lost their attachment to the extracellular matrix (ECM). Tumor cells that lose their connection to the ECM can die via apoptosis or survive via anoikis resistance and thus escaping to distant organs for metastatic progression. This review discusses the recent advances made in our understanding of the signaling effectors of anoikis in prostate cancer and the approaches to translate these mechanistic insights into therapeutic benefits for reducing lethal disease outcomes (by overcoming anoikis resistance). The prostate tumor microenvironment is a highly dynamic landscape wherein the balance between androgen signaling, cell lineage changes, epithelial-mesenchymal transition (EMT), extracellular matrix interactions, actin cytoskeleton remodeling as well as metabolic changes, confer anoikis resistance and metastatic spread. Thus, these mechanisms also offer unique molecular treatment signatures, exploitation of which can prime prostate tumors to anoikis induction with a high translational significance.Copyright © 2023 Nepali and Kyprianou.