Identifying a Therapeutic Partner for TAK228 for Pediatric Phase II Brain Tumor Studies
Co-investigators: Dr. Kristine Glunde, Dr. Barbara Slusher and Dr. Charles Eberhart
The goal of this proposal is to find new drugs that work together to kill pediatric brain tumor cells. As part of a previous Alex’s Lemonade Stand Foundation project, we found that a drug called TAK228 could kill pediatric brain tumor cells. This drug gets into the brain well and is currently in clinical trials in adults for breast and other cancer types. We found that TAK228 works well with some therapies we currently use in pediatric brain tumors. But those therapies may be too toxic for patients who have relapsed or refractory disease and who have already received heavy doses of chemotherapy and radiation.
We now propose to use our knowledge of the biology of TAK228 as well as the ways that cancer cell metabolism differs from normal cells to find new agents that could combine with TAK228 to kill pediatric brain tumor cells and spare normal cells. TAK228 is currently in the planning stages for a US-government-funded phase I study in pediatric brain tumors. At the end of this grant, we anticipate that we will have discovered at least one new drug that can be combined with TAK228 in phase II studies for patients with relapsed or refractory pediatric brain tumors.
Project Update 2020
We have identified two partners for the brain-penetrant mTOR inhibitor TAK228 and have demonstrated efficacy for these in vitro. We show that TAK228 synergizes with carboplatin in vivo in high-MYC medulloblastoma, suggesting this combination may be helpful for patients.