Oyende Yetunde, Taus Luke J, Fatatis Alessandro
Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA.
Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancers (Basel). 2025 Jan 17;17(2):290. doi: 10.3390/cancers17020290.
Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β synthesized and secreted by immune cells. Herein, we discuss the importance of IL-1β derived from cancer cells which impacts primary tumors, particularly metastatic lesions, separately from and in addition to its more recognized role in immune-mediated inflammatory events. To this end, we focus on the instrumental contribution of IL-1β in the establishment and progression of advanced prostate adenocarcinoma. Special emphasis is placed on the potential role that the standard-of-care treatment strategies for prostate cancer patients have in unleashing IL-1β expression and production at metastatic sites. We conclude by reviewing the therapeutics currently used for blocking IL-1β signaling and propose a rationale for their concomitant use with standard-of-care treatments to improve the clinical outcomes of advanced prostate cancer.
自发现以来，白细胞介素-1β（IL-1β）已成为围绕免疫介导和炎症事件的多种疾病的关键介质，处于核心地位。可以预见的是，这种细胞因子在人类病理学中的多效性导致了临床上具有多种治疗适应症的靶向治疗药物的开发。随着IL-1β在免疫系统中的核心调节作用以及炎症途径在癌症中的作用等研究结果的不断积累，IL-1β拮抗剂的使用首先被提出，随后也被用于肿瘤疾病的治疗。然而，这种方法一直依赖于干扰免疫细胞合成和分泌的IL-1β的需求。在此，我们讨论癌细胞来源的IL-1β的重要性，它对原发性肿瘤，特别是转移性病变产生影响，这一作用有别于且补充了其在免疫介导的炎症事件中更为人熟知的作用。为此，我们重点关注IL-1β在晚期前列腺腺癌的发生和发展中的作用。特别强调了前列腺癌患者的标准治疗策略在转移部位释放IL-1β表达和产生方面的潜在作用。我们通过回顾目前用于阻断IL-1β信号传导的治疗方法来得出结论，并提出将其与标准治疗联合使用以改善晚期前列腺癌临床结局的理论依据。
