Game Changer Grant Awarded to Nalin Gupta and Daniel Lim

Diffuse intrinsic pontine glioma (DIPG) is a lethal brain tumor of young children that arises in an extremely important part of the brain, marking surgical removal impossible. Although radiation therapy can slow the growth of this tumor, most children with DIPG die within two years of diagnosis. Despite decades of research, no other therapy has been found to be effective. Our long-term goal is to develop a treatment for DIPG that eliminates tumor cells without causing harm to the normal brain. Based on a number of recent discoveries – as well as our own data – we believe that targeting a new class of molecules called long noncoding RNAs (lncRNAs) provides a unique opportunity for us to achieve our goal. The cells in our bodies produce tens of thousands of different lncRNAs, and a small handful of these are required for cancer cells to grow. The key is to figure out which lncRNAs are the best targets for a drug. We recently developed the ability to rapidly test the function of thousands of lncRNAs. Using these “high-throughput” methods, we discovered which lncRNAs can be targeted to not only kill DIPG cells without causing harm to normal brain cells, but also enhance the efficacy of radiation. For one particular lncRNA target, we have also produced drugs suitable for use in human patients. In addition, we have developed a novel method for studying DIPG tumor growth in the brain that does not require doing experiments in living animals, which may accelerate drug development and reduce research costs. Completion of our proposed work is expected to provide data necessary to advance our therapy to clinical trials in children with DIPG. More generally, results obtained will provide new, fundamental insights into why cancer forms and how we might cure this disease.