SWCRF collaboration in action:

our scientists discover how mutated enzymes cause a deadly form of liver cancer.

 

Nabeel Bardeesy, Ph.D.,

Massachusetts General Hospital Harvard Medical School

Josep Llovet, M.D.,

Icahn School of Medicine at Mount Sinai

 

The Samuel Waxman Cancer Research Foundation congratulates its collaborating liver cancer researchers Nabeel Bardeesy, Ph.D., Gallagher Chair in Gastrointestinal Cancer Research at Massachusetts General Hospital and Josep Llovet, M.D., Director of the Liver Cancer Program at Icahn School of Medicine at Mount Sinai, whose benchmark findings on Intrahepatic cholangiocarcinoma were recently published in the leading science journal Nature.

Intrahepatic cholangiocarcinoma (ICC) is a deadly liver cancer that has increased in incidence for several decades and is among the most lethal of all human malignancies with an average survival period of less than one year. Recent work has identified mutations in the metabolic enzymes isocitrate dehydrogenase 1 or 2 (IDH1/2) as important genetic changes in this disease; however, how these mutations caused cancer remained unclear. 

The study by Drs. Bardeesy and Llovet provided important insights into the role of these two enzymes in liver cancer. The Mark Family support of the SWCRF Liver Cancer Research Program contributed to the funding of this collaboration, which revealed that mutations in the two enzymes block the expression of a gene called hepatocyte nuclear factor 4 alpha (HNF4a). Without this important gene, the liver’s own stem cells that arise during injury or with aging fail to mature into normal adult liver cells, or hepatocytes, and continue to multiply.

This collaborative work has not only begun to elucidate the origin of this challenging cancer, but it has also begun laying the groundwork for the development of therapies. By combining a mutant enzyme with a commonly mutated gene called Kras in a genetically engineered mouse model, our scientists went on to show how these cells progress in a step-wise manner from early pre-cancerous lesions to aggressive metastatic ICC tumors that mimic the human disease.  This new mouse model will enable future studies aimed at identifying and testing new therapies for this currently incurable malignancy. 

This project is yet another example of the productive cross-institutional collaborations borne out of the Institute Without Walls of the SWCRF and supported through our generous donors. Click here to support the SWCRF deliver new victories in cancer research.