Research Projects

The Mayo Clinic Pancreatic Cancer SPORE currently supports five translational research projects:

Targeting Fatty Acid Synthase: A Mechanism-Guided Approach to Target Pancreatic Adenocarcinoma and the Tumor Microenvironment

The leaders of this research project are Ruth Lupu, Ph.D., and Robert R. McWilliams, M.D.

The basis of this project is that aberrant activation of de novo lipogenesis by fatty acid synthase (FASN) plays a crucial role in promoting pancreatic cancer cell proliferation, survival and metastasis, while at the same time modulating the tumor microenvironment.

The goals of the project are to:

  • Determine the mechanism by which FASN inhibition induces the BH3-only proteins and sensitizes to gemcitabine
  • Determine the role of FASN in promoting a TGFβ-induced pro-tumorigenic microenvironment
  • Evaluate the effects of a novel FASN inhibitor, TVB-2640, in combination with standard chemotherapy in patients with metastatic pancreatic ductal adenocarcinoma (PDA cancer) by conducting a phase Ib/II clinical trial

Targeting Aberrant FGFR Signaling in Pancreatic Cancer

The leaders of this research project are Martin E. Fernandez-Zapico, M.D., and Tanios S. Bekaii-Saab, M.D.

The translational work in this project is supported by recent research by the project leaders demonstrating that FGFR alterations are prevalent in pancreatic cancer and that targeting these alterations with highly sensitive FGFR inhibitors could provide significant clinical benefit.

The goals of this project are to:

  • Define the epigenetic mechanisms downstream of activated FGFR signaling in pancreatic cancer
  • Characterize the responses of the pancreatic cancer models to FGFR inhibition in combination therapies
  • Perform a phase Ib clinical trial of BGJ398 in patients with advanced pancreatic cancer harboring FGFR alterations

Combination Therapy With Oncolytic Virus and CAR-T in Advanced Pancreatic Cancer

The leaders of this research project are Mitesh J. Borad, M.D., and Januario E. Castro, M.D.

The main goal of this translational project is to develop a safe and effective gene-immunotherapy platform that can be rapidly and efficiently translated to treat patients with advanced pancreatic cancer. The project leaders are using a novel adenovirus vector (Ad5NULL-A20) that has been modified to specifically transduce cells expressing avb6, which is overexpressed in pancreatic cancer.

The other goals of this project are to:

  • Evaluate in vivo the safety, toxicology, tolerability and biodistribution of Ad5NULL-A20 vectors encoding htCD19, SSTR2 and hyaluronidase (PH20)
  • Perform a first-in-human study of Ad5NULL-A20 encoding htCD19, SSTR2 and PH20 in patients with advanced pancreatic cancer
  • Evaluate in vivo the activity of Ad5NULL-A20 oncolytic vectors in combination with CAR-T cells

Modulation of the Tumor-Immune Microenvironment for the Treatment of Pancreatic Cancer

The leaders of this research project are Peter Storz, Ph.D., and Tanios S. Bekaii-Saab, M.D.

The hypothesis driving the translational research in this project is that pomalidomide can shift the tumor microenvironment from immune suppressive to immune responsive and that combination therapy will be more efficient for primary tumors and metastases.

The goals of this project are to:

  • Test pomalidomide in combination therapy with nanoliposomal irinotecan/5-fluorouracil on established murine tumors and metastases
  • Perform a pilot clinical trial to test if pomalidomide is efficient in combination therapy with standard nanoliposomal irinotecan/5-fluorouracil

Role of GSK-3 in DNA Repair and Therapeutic Implications in Pancreas Adenocarcinoma

The leaders of this research project are Daniel D. Billadeau, Ph.D., and Wen Wee Ma, M.B.B.S.

This project research team has previously shown that 9-ING-41, a GSK-3 inhibitor that is in the clinic, sensitizes pancreatic cancer cells to chemotherapy by targeting the ATR DNA damage repair pathway indirectly. The central hypothesis supporting this translational project is that GSK-3b activity plays a crucial role in regulating the response to DNA damage and that interruption will lead to reversal of chemoresistance and synthetic lethality in HRD repair-deficient pancreatic cancer.

The goals of the project are to:

  • Determine the mechanism by which GSK-3b regulates the stability of TopBP1
  • Define the impact of GSK-3 inhibition in PDA tumors lacking functional ATM-related DNA damage response pathways
  • Evaluate the effects of a novel GSK-3 inhibitor, 9-ING-41, in combination with nanoliposomal irinotecan in patients with metastatic pancreatic ductal adenocarcinoma by conducting a phase II clinical trial