Childhood Cancer

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Molecular circuitry of fibrolamellar carcinoma

Massachusetts General Hospital
Nabeel Bardeesy, PhD
Grant Type: 
Innovation Grants
Year Awarded: 
Type of Childhood Cancer: 
General Pediatric Cancer
Project Description: 

Fibrolamellar carcinoma is an liver cancer of adolescents and young adults. Currently the only effective treatment is surgery, but this is only possible in a subset of cases. Chemotherapy and targeted therapies have not been successful to date. Important features of this cancer include the presence of an abnormal gene in virtually every patient. This abnormal gene, referred to as DNAJB1-PRKACA, is found in virtually all patients. A key challenge is to understand how DNAJB1-PRKACA affect the growth of cancer cells, and in particular, to determine how important it is for full formed cancers to keep growing. Secondly, it is important to more broadly determine the set of genes required for fibrolamellar carcinomas to survive and grow. This information will guide the development of improved treatments for patients with this disease.

Project Goal:

The goal of this project is to build on recent observations from our group demonstrating that DNAJB1-PRKACA is indeed very important for the growth of fibrolamellar carcinoma. The study will explore in detail what are the associated biochemical mechanisms. We have identified multiple proteins that are controlled by DNAJB1-PRKACA and we have linked several of these to tumor growth and to a unique set of abnormalities in the mitochondria (the cell's energy factories) of fibrolamellar carcinomas. We expect these studies to identify several therapeutic strategies against these tumors.