Part of the well-known TGF- tumor suppressor pathway, the molecule disappears in the cells of nearly 90 percent of human hepatocellular cancers, the most common type of liver cancer. Lopa Mishra, MD, professor and vice chair in the department of surgery at Georgetown University Medical Center, showed that loss of only one copy of the embryonic liver fodrin, or ELF gene, can result in spontaneous development of liver cancer in human cell cultures and in vivo models.

In a paper published online by Oncogene on June 4, Mishra and her team also reported that by reintroducing ELF to the cancer cells, the proteins driving cell division and growth were kept in check. To the research team, this implies that ELF or another inhibitor of downstream cell division and growth proteins could be developed into an effective new therapy.

"We're looking for ways of treating untreatable cancers," explained Mishra. "Pancreatic and liver cancers are the third- and fourth-leading causes of cancer death in the world."

Hepatocellular cancer has a very low 5-year survival rate less than 5 percent and the incidence of the disease has risen in the United States over the past several years.

One difficulty in treating liver cancer is the variety of different mutations seen in among patients. The findings about ELF may indicate that it is a critical component that could be targeted to treat 90 percent of patients with this disease. Currently, only 12 percent of patients are eligible for surgery, and very few other treatment options are available.

Mishra's findings on the role of ELF in the development of liver cancer also suggest a method for preventing the disease. Because the cancer forms as a multistep process, beginning with cirrhosis and following a known progression, it's possible that the same ELF molecule can be targeted to pre-cancerous lesions in the liver.

gumc.georgetown

In addition, the method could be used one day in gene therapy. It may be possible to replace damaged proteins that cause severe diseases with genetically engineered proteins, and to control these proteins' activity levels in a precise manner by giving appropriate doses of the drug. Another potential future application is in agricultural genetic engineering. The method might make it possible, for example, to create genetically engineered plants in which the precise timing of fruit ripening would be controlled using a substance that increases the activity of proteins responsible for ripening. Moreover, numerous proteins are used in industrial processes, as biological sensors and in other applications. The possibility of controlling these applications “ strengthening or slowing the rate of protein activity in an immediate and reversible manner “ can be of great value.

Prof. Mordechai Liscovitch's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; La Fondation Raphael et Regina Levy; and the Estate of Simon Pupko, Mexico. Prof. Liscovitch is the incumbent of the Harold L. Korda Professorial Chair of Biology.

The Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

weizmann.ac.il/