Gong Li, Yang Shixue, Huang Junli, Li Yongsheng
Department of Phase I Clinical Trial Ward, Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing 400030, China.
Key Laboratory of Biorheological Science and Technology of Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, China.
Cancer Biol Med. 2024 Nov 25;21(12):1141-55. doi: 10.20892/j.issn.2095-3941.2024.0320.
The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment. Key oncogenic targets, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and kirsten rat sarcoma viral oncogene homologue (KRAS), have emerged as focal points in the development of targeted agents. Research has investigated the impact of gut microbiota on the efficacy of various anticancer therapies, such as immunotherapy, chemotherapy, and radiotherapy. However, a notable gap exists in the literature regarding the relationship between gut microbiota and targeted agents. This review emphasizes how specific gut microbiota and gut microbiota metabolites, including butyrate, propionate, and ursodeoxycholic acid, interact with oncogenic pathways to modulate anti-tumor effects. Conversely, deoxycholic acid, lipopolysaccharide, and trimethylamine n-oxide may exert pro-tumor effects. Furthermore, modulation of the gut microbiota influences glucose and lipid metabolism, thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors. By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways, this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.
全球癌症发病率的上升引发了人们对作为一种抗癌治疗形式的靶向治疗的浓厚兴趣。关键的致癌靶点，包括表皮生长因子受体（EGFR）、血管内皮生长因子（VEGF）和 Kirsten 大鼠肉瘤病毒致癌基因同源物（KRAS），已成为靶向药物开发的焦点。研究已经调查了肠道微生物群对各种抗癌疗法（如免疫疗法、化疗和放疗）疗效的影响。然而，关于肠道微生物群与靶向药物之间的关系，文献中存在明显的空白。本综述强调了特定的肠道微生物群和肠道微生物群代谢产物（包括丁酸、丙酸和熊去氧胆酸）如何与致癌途径相互作用以调节抗肿瘤作用。相反，脱氧胆酸、脂多糖和氧化三甲胺可能发挥促肿瘤作用。此外，调节肠道微生物群会影响葡萄糖和脂质代谢，从而增强对抗 KRAS 药物的反应，并解决酪氨酸激酶抑制剂引起的腹泻问题。通过阐明肠道微生物群与 EGFR/VEGF/KRAS 途径之间的联系，本综述为推进靶向癌症治疗和优化临床环境中的治疗结果提供了有价值的见解。
