Linking Gut Bacteria, Obesity, and Breast Cancer
It is known that obesity and diet affect cancer growth. Naturally occurring gut bacteria play key roles in the regulation of diet-based obesity. Principal Investigators Todd Miller, PhD and Craig Tomlinson, PhD, seek to understand whether and how gut bacteria communicate with cancer cells to influence their growth, which may be manipulated through changes in diet. The Aryl Hydrocarbon Receptor (AHR), best known for its roles in breakdown of toxins and immune system maturation, acts as a key signal transducer that may link diet, gut bacteria, obesity, and breast cancer. The team predicts that inhibition of the AHR will not only reduce obesity, but also tumor growth, which may involve changes in gut bacterial composition. “We will determine whether diet affects breast cancer growth, and whether this link involves gut bacterial composition and AHR signaling. AHR can be blocked by existing drugs, and gut bacterial composition can be modified by diet and pro-biotics, which would offer novel therapeutic approaches to treat cancer,” says Miller.
Connecting the Immune System and Virally Infected Cancer
Chao Cheng, PhD, and his team are characterizing immune response in virally induced tumors relative to tumors of the same type that are not caused by virus infection. Approximately 20 percent of cancers are associated with virus infection. “We are using computational tools that can use information in a patient’s genome to determine whether a patient’s tumor was due to a virus infection, infer the types of immune cells present at a patient’s tumor, and predict the factors that brought the cells to the tumor,” says Cheng. By better understanding how virus-associated cancers interact with the host immune system in a distinct manner relative to other cancer types, the team may be able to exploit them to predict therapy response and prolong patient survival. “Understanding these differences can better inform us about the types of therapy these tumors are likely to respond to and whether we can use the altered immune responses to the patient’s advantage.”
Eliminating Surgery in Some Esophageal Tumors
Principal investigators Bassem Zaki, MD, and Mikhail Lisovsky, MD, PhD, are using a genome-wide assessment of DNA copy number abnormalities to identify patients who may be able to avoid surgery as a step in the treatment of esophageal cancer. Some esophageal tumors have been shown to completely disappear after chemoradiation and before surgery. The team hypothesizes that these tumors will have a distinct combination of DNA abnormalities and that these abnormalities are the link to identifying other tumors that will also show excellent response to initial chemoradiation therapy and therefore do well without surgery. The approach could potentially eliminate surgery in 25–30 percent of patients.
De-escalating Surveillance Colonoscopy Among Older Adults
The research of Audrey Calderwood, MD, is focused on when and how to “de-escalate” monitoring among older adults with a history of colon polyps or colon cancer. “As older adults age and develop competing co-morbidities, the risks of surveillance colonoscopy can outweigh the benefits, potentially leading to unnecessary harm,” says Calderwood. “I suspect that we are overusing surveillance colonoscopy among older adults with a history of colon polyps and colon cancer and that if these adults were provided appropriate information on risks and benefits to guide their decision-making, a majority would likely opt out of ongoing colonoscopy.”
Mapping Pediatric Brain Tumors
Brock Christensen, PhD, and his team are aiming to draw higher resolution maps of epigenetic DNA alterations in pediatric brain tumors. By characterizing these alterations to DNA, they seek to understand their relationship with tumor subtypes as well as patient prognosis. Among pediatric brain tumor subtypes, the team hypothesizes that there will be both distinct and common patterns in the DNA alterations that they measure. “Our goal of measuring DNA alterations across subtypes of pediatric brain tumors will both increase our understanding of genes that are altered in cancer and potentially contribute to new avenues for designing and implementing treatments for this very aggressive disease,” says Christensen. “As of yet we have an incomplete understanding of the ways that epigenetic alterations to DNA contribute to disease progression in brain tumors, particularly pediatric tumors. By defining the patterns of tumor alterations, we hope to improve clinical care and uncover new ways to treat disease.”
The next round of pilot project awards funded by the 35th Prouty are expected to be announced this winter. The 37th annual Prouty will take place on July 13–14, 2018.