This review delves into the intricate roles of interleukin-8 (IL-8) and its receptors, CXCR1 and CXCR2, in prostate cancer (PCa), particularly in castration-resistant (CRPC) and metastatic CRPC (mCRPC). This review emphasizes the crucial role of the tumour microenvironment (TME) and inflammatory cytokines in promoting tumour progression and response to tumour cell targeting agents. IL-8, acting through C-X-C chemokine receptor type 1 (CXCR1) and type 2 (CXCR2), modulates multiple signalling pathways, enhancing the angiogenesis, proliferation, and migration of cancer cells. This review highlights the shift in PCa research focus from solely tumour cells to the non-cancer-cell components, including vascular endothelial cells, the extracellular matrix, immune cells, and the dynamic interactions within the TME. The immunosuppressive nature of the PCa TME significantly influences tumour progression and resistance to emerging therapies. Current treatment modalities, including androgen deprivation therapy and chemotherapeutics, encounter persistent resistance and are complicated by prostate cancer’s notably “immune-cold” nature, which limits immune system response to the tumour. These challenges underscore the critical need for novel approaches that both overcome resistance and enhance immune engagement within the TME. The therapeutic potential of inhibiting IL-8 signalling is explored, with studies showing enhanced sensitivity of PCa cells to treatments, including radiation and androgen receptor inhibitors. Clinical trials, such as the ACE trial, demonstrate the efficacy of combining CXCR2 inhibitors with existing treatments, offering significant benefits, especially for patients with resistant PCa. This review also addresses the challenges in targeting cytokines and chemokines, noting the complexity of the TME and the need for precision in therapeutic targeting to avoid side effects and optimize outcomes.
本综述深入探讨了白细胞介素-8（IL-8）及其受体CXCR1和CXCR2在前列腺癌（PCa），尤其是去势抵抗性前列腺癌（CRPC）和转移性去势抵抗性前列腺癌（mCRPC）中的复杂作用。重点强调了肿瘤微环境（TME）和炎症细胞因子在促进肿瘤进展及影响肿瘤细胞靶向药物疗效中的关键作用。IL-8通过C-X-C趋化因子受体1型（CXCR1）和2型（CXCR2）调控多条信号通路，从而增强癌细胞的血管生成、增殖和迁移能力。本文指出前列腺癌研究重点已从单纯关注肿瘤细胞转向非癌细胞成分，包括血管内皮细胞、细胞外基质、免疫细胞以及TME内的动态相互作用。前列腺癌TME的免疫抑制特性显著影响肿瘤进展及对新兴疗法的耐药性。当前的治疗方式，包括雄激素剥夺疗法和化疗药物，面临持续耐药性问题，且因前列腺癌显著的“免疫冷”特性而复杂化，这种特性限制了免疫系统对肿瘤的反应。这些挑战凸显了迫切需要开发既能克服耐药性又能增强TME内免疫参与的新策略。本文探讨了抑制IL-8信号通路的治疗潜力，研究表明该策略能增强前列腺癌细胞对放疗和雄激素受体抑制剂等治疗的敏感性。诸如ACE试验等临床试验证明，将CXCR2抑制剂与现有疗法联合使用具有显著疗效，尤其对耐药性前列腺癌患者带来重要获益。本综述还讨论了靶向细胞因子和趋化因子所面临的挑战，指出TME的复杂性以及需要精准治疗靶向以避免副作用并优化疗效。
肿瘤(癌症)患者之家