Chatterjee Annesha, Azevedo-Martins Jordana Maria, Stachler Matthew D
University of California San Francisco, Department of Pathology, San Francisco, CA, USA.
Onco Targets Ther. 2023 Aug 10;16:675-687. doi: 10.2147/OTT.S389120. eCollection 2023.
Gastric cancer is a significant global health problem as it is the fifth most prevalent cancer worldwide and the fourth leading cause of cancer-related mortality. While cytotoxic chemotherapy remains the primary treatment for advanced GC, response rates are limited. Recent progresses, focused on molecular signalling within gastric cancer, have ignited new hope for potential therapeutic targets that may improve survival and/or reduce the toxic effects of traditional therapies. Carcinomas are generally initiated when critical regulatory genes get mutated, but the progression to malignancy is usually supported by the non-neoplastic cells that create a conducive environment for transformation and progression to occur. Interleukin 33 (IL-33) functions as a dual activity cytokine as it is also a nuclear factor. IL-33 is usually present in the nuclei of the cells. Upon tissue damage, it is released into the extracellular space and binds to its receptor, suppression of tumorigenicity 2 (ST2) L, which is expressed on the membranes of the target cells. IL-33 signalling activates the T Helper 2 (Th2) immune response among other responses. Although the studies on the role of IL-33 in gastric cancer are still in the early stages, they have revealed potentially important (though sometimes conflicting) functions or roles in cancer development and progression. The pro-tumorigenic roles include induction and the recruitment of tumor-associated immune cells, promoting metaplasia progression, and inducing stem cell like and EMT properties in gastric cancer cells. Therapeutic interventions to disrupt these functions may provide a unique strategy for gastric cancer prevention and treatment. This review aims to provide a summary of the role of IL-33 in GC, state its multiple functions in relation to GC, and show potential avenues for promising therapeutic investigation.
胃癌是一个重大的全球健康问题，因为它是全球第五大常见癌症，也是癌症相关死亡的第四大主要原因。虽然细胞毒性化疗仍然是晚期胃癌的主要治疗方法，但缓解率有限。最近聚焦于胃癌分子信号传导的进展，为可能改善生存率和/或降低传统疗法毒性作用的潜在治疗靶点点燃了新的希望。癌症通常在关键调控基因发生突变时启动，但向恶性肿瘤的进展通常由非肿瘤细胞支持，这些细胞为转化和进展创造了有利环境。白细胞介素33（IL-33）作为一种双重活性细胞因子发挥作用，因为它也是一种核因子。IL-33通常存在于细胞核中。在组织损伤时，它释放到细胞外空间并与其受体——抑制肿瘤发生2（ST2）L结合，ST2L在靶细胞膜上表达。IL-33信号传导除其他反应外还激活辅助性T细胞2（Th2）免疫反应。尽管关于IL-33在胃癌中作用的研究仍处于早期阶段，但它们已经揭示了其在癌症发展和进展中潜在的重要（尽管有时相互矛盾）功能或作用。促肿瘤作用包括诱导和募集肿瘤相关免疫细胞、促进化生进展以及诱导胃癌细胞的干细胞样和上皮-间质转化特性。破坏这些功能的治疗干预可能为胃癌的预防和治疗提供独特策略。本综述旨在总结IL-33在胃癌中的作用，阐述其与胃癌相关的多种功能，并展示有前景的治疗研究的潜在途径。
