University of Arizona Cancer Center, GI Medical Oncology, Tucson, AZ 85724, USA.
Banner University Medical Center-University of Arizona, Tucson, AZ 85719, USA.
Int J Mol Sci. 2024 Mar 4;25(5):2985. doi: 10.3390/ijms25052985.
Gastrointestinal cancers represent one of the more challenging cancers to treat. Current strategies to cure and control gastrointestinal (GI) cancers like surgery, radiation, chemotherapy, and immunotherapy have met with limited success, and research has turned towards further characterizing the tumor microenvironment to develop novel therapeutics. Myeloid-derived suppressor cells (MDSCs) have emerged as crucial drivers of pathogenesis and progression within the tumor microenvironment in GI malignancies. Many MDSCs clinical targets have been defined in preclinical models, that potentially play an integral role in blocking recruitment and expansion, promoting MDSC differentiation into mature myeloid cells, depleting existing MDSCs, altering MDSC metabolic pathways, and directly inhibiting MDSC function. This review article analyzes the role of MDSCs in GI cancers as viable therapeutic targets for gastrointestinal malignancies and reviews the existing clinical trial landscape of recently completed and ongoing clinical studies testing novel therapeutics in GI cancers.
胃肠道癌症是治疗难度较大的癌症之一。目前治疗胃肠道 (GI) 癌症的策略,如手术、放疗、化疗和免疫疗法,收效甚微,研究已转向进一步阐明肿瘤微环境,以开发新的治疗方法。髓源性抑制细胞 (MDSC) 已成为 GI 恶性肿瘤肿瘤微环境中发病机制和进展的关键驱动因素。许多 MDSC 的临床靶点在临床前模型中已经得到了定义,这些靶点可能在阻断募集和扩张、促进 MDSC 向成熟髓样细胞分化、消耗现有的 MDSC、改变 MDSC 代谢途径以及直接抑制 MDSC 功能方面发挥重要作用。本文分析了 MDSC 在胃肠道癌症中的作用,将其作为胃肠道恶性肿瘤的可行治疗靶点,并回顾了最近完成和正在进行的临床试验中测试胃肠道癌症新型治疗方法的临床研究现状。