Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dúbravská Cesta 9, 845 05 Bratislava, Slovakia.
Department of Genetics, Faculty of Natural Sciences, Comenius University, 842 15 Bratislava, Slovakia.
Int J Mol Sci. 2022 Jan 1;23(1):488. doi: 10.3390/ijms23010488.
Understanding the mechanisms of resistance to therapy in human cancer cells has become a multifaceted limiting factor to achieving optimal cures in cancer patients. Besides genetic and epigenetic alterations, enhanced DNA damage repair activity, deregulation of cell death, overexpression of transmembrane transporters, and complex interactions within the tumor microenvironment, other mechanisms of cancer treatment resistance have been recently proposed. In this review, we will summarize the preclinical and clinical studies highlighting the critical role of the microbiome in the efficacy of cancer treatment, concerning mainly chemotherapy and immunotherapy with immune checkpoint inhibitors. In addition to involvement in drug metabolism and immune surveillance, the production of microbiota-derived metabolites might represent the link between gut/intratumoral bacteria and response to anticancer therapies. Importantly, an emerging trend of using microbiota modulation by probiotics and fecal microbiota transplantation (FMT) to overcome cancer treatment resistance will be also discussed.
了解人类癌细胞对治疗的耐药机制已成为癌症患者实现最佳治愈的多方面限制因素。除了遗传和表观遗传改变外，增强的 DNA 损伤修复活性、细胞死亡的失调、跨膜转运蛋白的过度表达以及肿瘤微环境内的复杂相互作用，最近还提出了其他癌症治疗耐药机制。在这篇综述中，我们将总结临床前和临床研究，强调微生物组在癌症治疗（主要是化疗和免疫检查点抑制剂免疫治疗）中的关键作用。除了参与药物代谢和免疫监测外，微生物组衍生代谢物的产生可能代表了肠道/肿瘤内细菌与抗肿瘤治疗反应之间的联系。重要的是，还将讨论利用益生菌和粪便微生物移植（FMT）来调节微生物组以克服癌症治疗耐药性的新兴趋势。
