Targeting glioblastoma's resistance to cell death
Project 2: Overcoming drug-induced resistance to intrinsic apoptosis in glioblastoma
This work is trying to see whether adding a drug that blocks BCL-xL can help radiation, temozolomide, or a brain-penetrant EGFR inhibitor kill glioblastoma tumors.
Quick facts
| Grant type | NIH-funded research |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of California Los Angeles NIH-funded |
| Lab location | 1 site (Los Angeles, United States) |
| Project ID | NIH-11377159 on NIH RePORTER |
What this research studies
From a patient perspective, researchers first analyze large numbers of glioblastoma tumor samples using genetic tests and a functional BH3 profiling assay to find the molecular blocks that keep tumor cells alive. They will test a new BCL-xL antagonist (developed with AbbVie) in laboratory and animal models combined with standard radiation/temozolomide or a brain-penetrant EGFR inhibitor to see if the combinations cause more tumor cell death. The project includes a short "window of opportunity" clinical trial to look for early signs that the BCL-xL drug reaches the tumor and affects the cell-death pathway in people. The overall aim is to overcome a stubborn survival mechanism in GBM so standard treatments can work better.
Who could benefit from this research
Good fit: People with glioblastoma — especially those eligible for standard radiation plus temozolomide or EGFR-targeted treatment, and who can participate in a short pre-surgical or early clinical "window" trial — would be ideal candidates.
Not a fit: Patients with other types of brain tumors, or whose tumors lack the BCL-xL survival mechanism or who are medically ineligible for the drug combinations, may not benefit from this approach.
Why it matters
Potential benefit: If successful, this approach could make standard therapies kill more glioblastoma cells, potentially shrinking tumors and improving outcomes for patients.
How similar studies have performed: Prior preclinical work and earlier SPORE findings support the idea that targeting BCL family proteins can sensitize tumors to cell death, but combining a brain-penetrant BCL-xL antagonist with TMZ/IR or EGFR TKIs in GBM is a relatively new, early-stage strategy.
Where this research is happening
Los Angeles, United States
- University of California Los Angeles — Los Angeles, United States (Active)
Researchers
- Principal investigator: Nathanson, David a. — University of California Los Angeles
- Study coordinator: Nathanson, David a.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.