Abstract
Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. Mouse models are a valuable resource for use throughout the development and testing of new therapeutic strategies for CRC. Tumorigenesis and response to therapy in humans and mouse models alike are influenced by the microbial communities that colonize the gut. Differences in the composition of the gut microbiota can confound experimental findings and reduce the replicability and translatability of the resulting data. Despite this, the contribution of resident microbiota to preclinical tumor models is often underappreciated. This review does the following: (1) summarizes evidence that the gut microbiota influence CRC disease phenotypes; (2) outlines factors that can influence the composition of the gut microbiota; and (3) provides strategies that can be incorporated into the experimental design, to account for the influence of the microbiota on intestinal phenotypes in mouse models of CRC. Through careful experimental design and documentation, mouse models can continue to rapidly advance efforts to prevent and treat colon cancer.
Highlights
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide [1]. research advances during the past decade have led to some of the most exciting breakthroughs in cancer treatment, including immune checkpoint blockade, the majority of CRC cases fail to respond to these new therapies [2,3]
Despite mounting evidence for the critical role the resident microbiota play in influencing the frequency of tumor initiation, rate of progression, and response to therapy, there is an underappreciation for these factors when selecting and developing animal models of CRC
The present review provides mounting evidence that the bacteria that colonize the mammalian gut play a pivotal role in tumorigenesis and the response to therapy in classic mouse models of CRC (Table 1)
Summary
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths worldwide [1]. A critical need exists to develop new strategies for the early detection, prevention, and treatment of colorectal cancer, as well as to elucidate the basis for the ineffectiveness of existing therapies Such studies rely heavily on preclinical in vivo models that recapitulate the biology of human disease. Studies in both chemically induced and genetically engineered mouse models of CRC have enhanced our understanding of colon tumor initiation, progression, and response to therapy. Despite mounting evidence for the critical role the resident microbiota play in influencing the frequency of tumor initiation, rate of progression, and response to therapy, there is an underappreciation for these factors when selecting and developing animal models of CRC. Strategies are presented that investigators can employ to improve reproducibility and translatability of findings from mouse models of colon tumorigenesis and control factors that influence the composition of the microbiota
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