Wayne State University, Karmanos Cancer Institute, Detroit
Fridman is a scientific member of the Tumor and Microenvironment Program at the Karmanos Cancer Institute and a professor in the Department of Pathology at Wayne State University’s School of Medicine. Fridman’s research, in collaboration with Howard Crawford (above), is to investigate the role of fibrosis in pancreatic cancer with a focus on cancer cell-collagen interactions. The project is expected to explain the regulation and role of the Discoidin Domain Receptors (DDRs).
In addition, the study is expected to uncover the likely major contribution of collagen to tumor behavior and progression. Fibrosis and the associated collagen have been shown to act as critical barriers to delivery of therapeutic drugs.
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RESEARCH FUNDED BY SKY FOUNDATION, INC.
PROJECT TITLE: TARGETING COLLAGEN-INITIATED PRO-MALIGNANT PROGRAMS IN PANCREATIC CANCER
PRINCIPLE INVESTIGATORS:
Rafael Fridman, Ph.D., Professor, Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Institute, Detroit
Howard Crawford, Ph.D., Professor, Molecular & Integrative Physiology, and Internal Medicine. Director, Pancreas Research Program, University of Michigan, Ann Arbor
PROJECT SUMMARY:
The five-year survival of Pancreatic Ductal Adenocarcinoma (PDAC) patients is a dismal 9%, emphasizing the urgent need for new therapies
One of the striking hallmarks of PDAC is the intense collagen-rich fibrotic scar tissue within the tumor. In PDAC, the fibrotic tissue is associated with disease aggressiveness, including promotion of tumor growth, drug resistance, and metastasis
The aim is to suppress the pro-malignant effects of collagen in PDAC. The collaborative research focuses on a unique set of receptors known as the Discoidin Domain Receptors (DDR), which send pro-tumor signals in response to collagen, such as that found in PDAC
Fridman and Crawford hypothesize that targeting DDR activity in PDAC will suppress the pro-malignant effects of the collagen-rich environment and improve patient outcome
Consistent with this premise, previous and ongoing studies in their labs have identified DDR1 as a key player in the progression of PDAC in a mouse model that recapitulates human pancreatic cancer progression
Tumor progression is significantly impeded in mice engineered with no DDR1 gene
The researchers have now obtained a small molecule inhibitor of DDR1 and plan to use it in mouse models to test if this drug increases the lifespan of mice with pancreatic cancer by inhibiting tumor progression and metastasis