Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Department of Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA.
Curr Med Chem. 2024;31(40):6556-6571. doi: 10.2174/0109298673273303231208071403.
Prostate cancer (PCa) is the most frequent and second-lethal cancer among men. Despite considerable efforts to explore treatments like autologous cellular immunotherapy and immune checkpoint inhibitors, their success remains limited. The intricate tumor microenvironment (TME) and its interaction with the immune system pose significant challenges in PCa treatment. Consequently, researchers have directed their focus on augmenting the immune system's anti-tumor response by targeting the STimulator of the Interferon Genes (STING) pathway. The STING pathway is activated when foreign DNA is detected in the cytoplasm of innate immune cells, resulting in the activation of endoplasmic reticulum (ER) STING. This, in turn, triggers an augmentation of signaling, leading to the production of type I interferon (IFN) and other pro-inflammatory cytokines. Numerous studies have demonstrated that activation of the STING pathway induces immune system rejection and targeted elimination of PCa cells. Researchers have been exploring various methods to activate the STING pathway, including the use of bacterial vectors to deliver STING agonists and the combination of radiation therapy with STING agonists. Achieving effective radiation therapy with minimal side effects and optimal anti-tumor immune responses necessitates precise adjustments to radiation dosing and fractionation schedules. This comprehensive review discusses promising findings from studies focusing on activating the STING pathway to combat PCa. The STING pathway exhibits the potential to serve as an effective treatment modality for PCa, offering new hope for improving the lives of those affected by this devastating disease.
前列腺癌（PCa）是男性中最常见和第二致命的癌症。尽管人们做出了很大的努力来探索自体细胞免疫疗法和免疫检查点抑制剂等治疗方法，但它们的成功仍然有限。复杂的肿瘤微环境（TME）及其与免疫系统的相互作用在 PCa 治疗中带来了重大挑战。因此，研究人员专注于通过靶向 STimulator of the Interferon Genes（STING）途径来增强免疫系统的抗肿瘤反应。当先天免疫细胞的细胞质中检测到外源 DNA 时，STING 途径被激活，导致内质网（ER）STING 的激活。这反过来又触发了信号的增强，导致 I 型干扰素（IFN）和其他促炎细胞因子的产生。许多研究表明，激活 STING 途径会诱导免疫系统排斥和靶向消除 PCa 细胞。研究人员一直在探索各种激活 STING 途径的方法，包括使用细菌载体传递 STING 激动剂以及将放射疗法与 STING 激动剂结合使用。为了实现具有最小副作用和最佳抗肿瘤免疫反应的有效放射治疗，需要对放射剂量和分割方案进行精确调整。这篇全面的综述讨论了专注于激活 STING 途径来对抗 PCa 的研究中的有前途的发现。STING 途径有潜力成为 PCa 的有效治疗方式，为改善受这种毁灭性疾病影响的人们的生活带来了新的希望。
