Research

The Gastrointestinal Cancer Program studies a wide range of cancers that affect the gastrointestinal system, including pancreas cancer, liver cancer, esophagus cancer and colon cancer.

Our program also participates in the Mayo Clinic Hepatobiliary SPORE and the Mayo Clinic Pancreatic Cancer SPORE. The hepatobiliary SPORE — the first of its kind in the nation — conducts research to improve the diagnosis and treatment of liver cancer and bile duct cancer. The pancreatic SPORE promotes research focused on understanding the causes of pancreatic cancer and the pathways by which pancreatic cancer progresses.

The Gastrointestinal Cancer Program focuses on research in four main areas:

  • Investigating novel approaches for early detection of gastrointestinal malignancies, with a focus on luminal cancers
  • Identifying and evaluating novel biomarkers for prognostic stratification and prediction of therapeutic outcomes
  • Examining the role of the tumor microenvironment, including the role of the gut microbiome in the initiation and progression of gastrointestinal malignancies
  • Developing and testing individualized treatment approaches against novel therapeutic targets

Investigating novel approaches for early detection of gastrointestinal malignancies, with a focus on luminal cancers

Our research advances in this focus area include:

  • Developing a noninvasive method for early detection of colorectal cancer. Our researchers developed a multitarget stool DNA test and licensed the test to Exact Sciences for commercialization as Cologuard. In a large clinical trial, Cologuard demonstrated a 92% detection rate for colorectal cancer. Cologuard received approval from the Food and Drug Administration as a clinical screening test in 2014, and Medicare coverage followed. Cologuard is helping increase colorectal cancer screening rates in the general population. It's also helping colorectal screening reach underserved populations, including Alaska Native people, who have the highest incidence of colorectal cancer in the United States. Our researchers are now developing a similar noninvasive method for early detection of hepatobiliary malignancies.
  • Showing that in a community setting, unsedated techniques are acceptable, feasible and safe alternatives to sedated esophagogastroduodenoscopy in screening for Barrett's esophagus, a precursor to esophageal cancer.

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Identifying and evaluating novel biomarkers for prognostic stratification and prediction of therapeutic outcomes

Our research advances in this focus area include:

  • Demonstrating that in patients with recurrent colorectal cancer, those with microsatellite instability caused by deficient DNA mismatch repair tumors have a better outcome, unless there is an associated BRAFV600E mutation
  • Characterizing a set of FGFR mutations in intrahepatic cholangiocarcinoma and defining its response to FGFR inhibitors, ponatinib and BGJ398
  • Identifying a new biomarker that uses the levels of plasma thrombospondin-2 (THBS2) and CA19-9 measured by conventional ELISA for the early detection of patients at high risk of pancreatic ductal adenocarcinoma

Examining the role of the tumor microenvironment, including the role of the gut microbiome in the initiation and progression of gastrointestinal malignancies

Our research advances in this focus area include:

  • Defining a new set of pancreatic ductal adenocarcinoma drivers, including SMAD4, ZNF521 and FHIT, using a combination of mate pair and RNA sequencing.
  • Showing that patients with adenomas have gut microbiota distinct from participants without adenomas. This altered microbiome profile in patients with adenoma is predicted to increase primary and secondary bile acid production that supports the growth of bile-tolerant microbes, which in turn produces genotoxic or inflammatory metabolites promoting adenoma and colorectal cancer development.
  • Demonstrating that Hedgehog signaling may play a dual role in pancreatic cancer, acting as an oncogene in the early stages of disease and acting as a tumor-suppressor in the late stages of disease.

Developing and testing individualized treatment approaches against novel therapeutic targets

Our research advances in this focus area include:

  • Developing the first phase III immunotherapy adjuvant clinical trial in stage III colon cancer to evaluate the efficacy of the anti-PD-L1 antibody atezolizumab combined with FOLFOX versus FOLFOX alone in patients with d-MMR. This clinical trial also provides a unique opportunity to identify predictive biomarkers and includes an analysis of the microbiome and metabolome.
  • Showing that shorter-duration chemotherapy is an acceptable treatment option in the postoperative management of patients with stage III colon cancer.
  • Developing a strategy to assess the role of FGFR inhibitors in patients with advanced or metastatic FGFR-altered cholangiocarcinoma who progressed on or are intolerant of platinum-based chemotherapy.

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