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2017 Research Grant Award Spotlight: Popov, “Integrin AVB6 as a Therapeutic Target for Primary Sclerosing Cholangitis – Associated Cholangiocarcinoma”

PSC Partners Seeking a Cure


Each year, PSC Partners asks research grant awardees to share a layman’s summary as part of the process for accepting the grant.  We are excited to share the 2017 PSC-related research grant summaries with you! In order to make this information more digestible and shine a light on each individual study, we will share one summary per week until we’ve shared the details for all of them.  Please feel free to add your comments or thoughts at the bottom of each of these summaries for the researchers

Title: Integrin AVB6 as a Therapeutic Target for Primary Sclerosing Cholangitis – Associated Cholangiocarcinoma

Principal Investigator: Yury V. Popov, MD, PhD, Director, Liver Fibrosis Research, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA

Cholangiocarcinoma (CCA) is a liver and bile duct cancer of unknown cause and rising incidence worldwide. CCA is a devastating complication of PSC, difficult to diagnose and associated with high mortality. Treatment options are extremely limited as PSC-associated CCA patients often do not qualify for liver transplantation. In the absence of drug options in the treatment of PSC-associated CCA, poor prognosis and high mortality, new therapeutic approaches are urgently needed.

Integrin αvβ6 is an epithelial tissue cell surface receptor which is virtually absent from normal livers. It has been shown to be markedly upregulated on activated bile duct epithelial cells and liver cells with features of ductular transformation, correlating with fibrosis stage, both in rodent models of fibrosis and in patients with chronic liver disease. Integrin αvβ6 binds and activates transforming growth factor beta and is expressed on liver progenitor cells that are linked to both biliary fibrosis and the formation of cancer

This study proposes to develop a model of CCA in a mouse model of PSC (mdr2-/- ) and to assess the impact of integrin αvβ6 on the development of CCA and possible therapeutic potential of drugs targeting this pathway. Since several αvβ6-specific inhibitors are currently at various stages of drug development for other indications, rapid translation of findings into clinical practice is feasible.

 

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