Big Ideas

Aniruddha Deshpande, Ph.D.

Leukemias are the leading cause of cancer-related death in children. Even among the large and growing proportion of children who survive leukemia, there is a dire need for new, gentler therapies that can reduce the debilitating side effects of treatment.

Aniruddha Deshpande, Ph.D., and colleagues at the Sanford Burnham Prebys Medical Discovery Institute in La Jolla, Calif., aim to give more children a fighting chance by focusing on a particular mistake some cells make when manufacturing proteins from genes. Their research could open doors to better treatments, not only for pediatric leukemias, but potentially for cancers across the board.

The Importance of Fusion Proteins

A fusion protein happens when two genes fuse together and take on a life of their own. This fusion creates wayward proteins that take the brakes off of cell proliferation, causing cells to grow uncontrollably. In other words … cancer.

Deshpande and his team are studying how fusion proteins differ from normal, individual proteins. “First, we use genetic tools to find out what genes are important,” said Deshpande. “Then, we try to find drugs that can reverse this oncogenic programming.”

This exciting work was made possible in part when Deshpande received a V Scholar Grant in 2016, which was funded by the V Foundation Wine Celebration.

“If you identified a drug that could specifically target a fusion protein that is there in your cancer but absent in normal cells, then you have a therapeutic window where you would selectively kill tumor cells but spare normal cells, which is the essential thing that you need to do to reduce the toxicity of drugs,” said Deshpande.

New Discoveries Lead to More Effective Treatments

The good news is many of the drugs that target these fusion proteins already exist. What’s more, researchers have recently discovered that fusion proteins occur in many other types of cancer, not only blood cancers. This means fusion protein targeting drugs could bring better, gentler treatment options for patients with a wide range of cancer types.

“If you find that a patient has a certain type of fusion and if there is a drug that targets it, you know almost immediately that you have the potential to see a tremendous response that you otherwise might not see,” said Deshpande. “One of the things people are looking for is a treatment that can kill only cancer cells while sparing normal cells. These offer a really wonderful possibility because you don’t have these fusions in normal, non-cancerous cells.”