Section Pathology of the Institute of Forensic Medicine, University Hospital Jena, Friedrich Schiller University Jena, Am Klinikum 1, 07747 Jena, Germany.
Int J Mol Sci. 2021 Jun 10;22(12):6262. doi: 10.3390/ijms22126262.
Colorectal carcinoma (CRC) is one of the most frequently diagnosed carcinomas and one of the leading causes of cancer-related death worldwide. Metabolic reprogramming, a hallmark of cancer, is closely related to the initiation and progression of carcinomas, including CRC. Accumulating evidence shows that activation of oncogenic pathways and loss of tumor suppressor genes regulate the metabolic reprogramming that is mainly involved in glycolysis, glutaminolysis, one-carbon metabolism and lipid metabolism. The abnormal metabolic program provides tumor cells with abundant energy, nutrients and redox requirements to support their malignant growth and metastasis, which is accompanied by impaired metabolic flexibility in the tumor microenvironment (TME) and dysbiosis of the gut microbiota. The metabolic crosstalk between the tumor cells, the components of the TME and the intestinal microbiota further facilitates CRC cell proliferation, invasion and metastasis and leads to therapy resistance. Hence, to target the dysregulated tumor metabolism, the TME and the gut microbiota, novel preventive and therapeutic applications are required. In this review, the dysregulation of metabolic programs, molecular pathways, the TME and the intestinal microbiota in CRC is addressed. Possible therapeutic strategies, including metabolic inhibition and immune therapy in CRC, as well as modulation of the aberrant intestinal microbiota, are discussed.
结直肠癌（CRC）是最常见的癌症之一，也是全球癌症相关死亡的主要原因之一。代谢重编程是癌症的一个标志，与包括 CRC 在内的癌症的发生和发展密切相关。越来越多的证据表明，致癌途径的激活和肿瘤抑制基因的失活调节了主要涉及糖酵解、谷氨酰胺分解、一碳代谢和脂质代谢的代谢重编程。异常的代谢程序为肿瘤细胞提供了丰富的能量、营养物质和氧化还原需求，以支持其恶性生长和转移，同时伴随着肿瘤微环境（TME）中代谢灵活性的受损和肠道微生物群落的失调。肿瘤细胞、TME 成分和肠道微生物群落之间的代谢串扰进一步促进了 CRC 细胞的增殖、侵袭和转移，并导致治疗耐药性。因此，需要针对失调的肿瘤代谢、TME 和肠道微生物群落，开发新的预防和治疗应用。在这篇综述中，探讨了 CRC 中代谢程序、分子途径、TME 和肠道微生物群落的失调。讨论了可能的治疗策略，包括 CRC 中的代谢抑制和免疫治疗，以及对异常肠道微生物群落的调节。
