Until recently, the role of microorganisms in the tumor microenvironment - the cellular environment surrounding the tumor, including blood vessels, immune cells, fibroblasts, etc. - was poorly understood. However, recent studies have highlighted the roles of specific bacterial species in promoting chemoresistance.
Colorectal Cancer
Advanced colorectal cancer (CRC) patients are commonly treated with the chemotherapeutic agents 5-fluoruracil, capecitabine, and oxaliplatin. While patients generally respond favorably to initial treatment, tumor recurrence may occur due to the development of drug resistance. Fusobacterium nucleatum was recently reported to track with post-chemotherapy recurrence and was found to promote changes in the host immune response that cause chemoresistance.
Our group is using human microbiota-associated microbiota mouse models, in collaboration with the Subree lab, to determine whether CRC-specific human microbial communities are similarly able to confer chemoresistance. We hope to find novel species and/or patterns of microbial species distributions that indicate chemoresistance and can be used to develop microbiota-targeted therapies to improve patient responses.
Pancreatic Cancer
Pancreatic cancers have recently surpassed breast cancers as the third leading cause of cancer mortality with a 5-year survival rate of only 8.5%. Of particular concern is the high resistance of some tumors to chemotherapeutic treatments that may increase the chance of success surgical resection. While previously thought to be sterile, a bacterial component was recently identified in the microenvironment of pancreatic ductal adenocarcinomas (PDAC) and, to a much lesser extent, healthy pancreatic tissue. In particular, members of class Gammaproteobacteria were recently found to be able to actively metabolize a commonly used chemotherapeutic agent, gemcitabine, as well as oxaliplatin.
Our group is working with surgical oncologists Drs. Eric Jensen and Jacob Ankeny to better characterize the microbiota associated with PDAC and identify signatures in the community that are predictive of the success of chemotherapy. Our goal is to develop personalized, multimodal therapies that increase the efficacy of chemotherapies and lead to improved surgical outcomes and longer survival.
Recent Presentations and Publications
- Khan MH, Onyeaghala G, Rashidi A, Holtan SG, Khoruts A, Israni A, Jacobson PA*, Staley C*. 2022. Fecal β-glucuronidase activity differs between hematopoietic cell and kidney transplantation and a possible mechanism for disparate dose requirements. Gut Microbes 14(1), 2108279. doi:10.1080/19490976.2022.2108279
- Saqr A, Carlson B, Staley C, Rashidi A, Al-Kofahi M, Kaiser T, Holtan S, MacMillan M, Young J-A, El Jurdi, N, Wesidorf D, Khoruts A, Jacobson P. 2022. Reduced enterohepatic recirculation of mycophenolate and lower blood concentrations are associated with the stool bacterial microbiome after hematopoietic cell transplantation. Transplant Cell Ther. 28(7), 372.e1-372.e9. doi:10.1016/j.jtct.2022.04.018
- Nalluri H, Jensen E, Staley C. 2021. Role of biliary stent and neoadjuvant chemotherapy in the pancreatic tumor microbiome. BMC Microbiol. 21(1), 280. doi:10.1186/s12866-021-02339-3
- Nalluri H, Staley C, Jensen EH. A Correlation between Biliary Stents and Pancreatic Tumor Microbiome, 2020 Fall Conference Minnesota Surgical Society