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Author: Sophia
Introduction: Preoperative neoadjuvant chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, but little is known about the mediators behind heterogeneous patient responses.
On December 23, 2022, Peking University Cancer Hospital Academician Zhan Qimin's research group and Professor Wang Weihu's team collaborated to publish a paper "Gut microbiota-mediated nucleotide synthesis attenuates the response to neoadjuvant chemoradiotherapy in rectal cancer" in "Cancer Cell". From the perspective of host-bacteria interaction, it revealed the molecular basis of the impact of intestinal microorganisms on the efficacy of neoadjuvant chemoradiotherapy in locally advanced rectal cancer..
https://www.sciencedirect.com/science/article/pii/S1535610822005608
Research background
01
Rectal cancer is one of the leading causes of cancer-related death in the world, accounting for 3.2% of all cancer-related deaths. More than 700,000 new cases of rectal cancer are diagnosed globally every year, and more than 30% of them are diagnosed at an advanced stage with poor survival. 2 Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision has become the established standard treatment for locally advanced rectal cancer (LARC). However, only 15%–27% of patients receiving nCRT achieve pathological complete response, and 720%–40% have almost no response. Therefore, efforts to decipher the mechanisms of LARC response to nCRT are urgently needed.
As a key participant in host metabolism, symbiotic microorganisms in the lumen of the human gastrointestinal tract co-evolve with the host in a mutually beneficial relationship. Increasing evidence suggests that the gut microbiota is closely related to the development and progression of colorectal cancer in multiple ways through inflammation and immune responses, and its composition has also been reported to influence tumor sensitivity to cancer treatments .
Research Progress
02
In this study, the researchers performed 16S rRNA amplicon sequencing on 353 stool specimens prospectively collected from 126 Chinese LARC patients, to determine changes in the microbiota corresponding to chemoradiation and chemotherapy, , and performed metatranscriptome sequencing, metabolite analysis, and in vitro and in vivo functional validation, to decipher the mechanisms by which rectal cancer cells respond to the effects of chemoradiotherapy..
The researchers first explored the impact of nCRT on the overall microbial community composition in fecal samples from LARC patients by performing permutational multivariate analysis of variance on the Bray-Curtis distance. To further dissect changes in the fecal microbiota corresponding to chemotherapy, the researchers assessed bacterial abundance between groups and observed considerable differences in the gut microbiota between samples from each group. Integration of
multi-omics data shows that C. exosus-mediated nucleotide biosynthesis is associated with nCRT resistance in LARC patients, and non-responsive tumors are characterized by upregulation of DNA repair and nucleoside transport-related genes. Nucleoside supplements or B. Epidermal gavage protects cancer cells from 5-fluorouracil or irradiated treatment. Analysis of 2,205 serum samples from 735 patients demonstrated uric acid as a potential prognostic marker in LARC patients receiving nCRT.
Significance of the study
03
In conclusion, the researchers here propose the concept that the response of rectal tumors to chemotherapy can be modulated by gut microbiota-mediated nucleotide biosynthesis. The study data highlight the importance of considering the crosstalk between cancer cells and the gut microbiota to gain a deeper understanding of the mechanisms of cancer patients' response to clinical treatments.
Reference:
https://www.sciencedirect.com/science/article/pii/S1535610822005608
Note: This article is intended to introduce the progress of medical research and cannot be used as a reference for treatment plans. If you need health guidance, please go to a regular hospital.
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