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Gut Microbiome as a Predictor of Response to Chemotherapy in Metastatic Colorectal Cancer

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[Technical Report, Annual Report]

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Despite decades of research, a combination of cytotoxic chemotherapies continues to be the first line treatment for metastatic colon and rectal cancer CRC. Patients typically respond variably to chemotherapy with 20-30 experiencing only disease stability and up to 30 progressing despite chemotherapy. Currently there are no known and validated predictors of response to cytotoxic chemotherapy. Furthermore, whether there are any patient related factors, which predict response to chemotherapy, is not known. Recent years have seen an increase in our understanding of the role of gut microbiome in health as well as in the pathogenesis of various diseases. Recent research from our group and others have shown that gut microbiota supports growth of colon, pancreatic and many other cancers. Our preliminary studies also suggest that not all the bacterial communities in gut microbiome promote tumor growth as selective gut microbiome modulation by individual antibiotics like vancomycin or metronidazole has similar effects Interestingly, our preliminary data in animal models suggest that gut microbiome can modulate response of cancer to various therapeutic strategies including chemotherapy and immunotherapy. This interaction of gut microbiome and chemotherapy in the treatment of colon cancer has been observed by other groups as well. For instance, it has been observed that in the absence of gut microbiome the efficacy of Oxaliplatin is reduced and this may be due partially to an impaired ROS production by myeloid cells. Based on literature as well as our preliminary studies we have proposed a novel hypothesis Gut microbiome composition can predict response of patients with metastatic colorectal cancer to standard of care chemotherapy.

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  • Medicine and Medical Research

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[A, Approved For Public Release]