Supported Research

Synthetic Lethal Approaches to Treatment of FA Gene Mutant Head and Neck Cancer


Amount Funded: $250,000

Head and neck cancer in adult Fanconi anemia patients is often poorly managed with standard treatments. New drugs that work on controlling the cell cycle and cell division, rather than by damaging the cell’s DNA, may be safer in patients with FA. Researchers have preliminary evidence that combinations of these drugs are active in head and neck cancer. Using head and neck cancers that have mutations in Fanconi genes, researchers propose to test whether these combinations can kill cancer cells with Fanconi gene mutations as a way to decide whether to test them in patients with FA. Dr. Burtness will also engage with Dr. Erica Golemis at the Fox Chase center and Caris Life Sciences to have access to a significant bio-repository and genomic information that will accelerate the research program.

See the grant’s outcomes, concluded in 2024. Summary from the final report:

The goals of Dr. Burtness and Dr. Kupfer’s study were to identify and validate FA gene mutations in head and neck squamous cell carcinoma (HNSCC), develop pre-clinical models using a subset of the HNSCC from aim one with validated FA gene mutations, and test for the efficacy of drugs targeting the pathways that are specifically vulnerable in FA mutant cells using the preclinical models developed in aim two. Their work has illuminated at least two avenues whereby head and neck cancer containing Fanconi gene defects can be targeted by capitalizing on the underlying biology of the pathway. One strategy utilizes existing drugs that will be tested imminently and can lead shortly to use in a clinical trial, while the other involves the development of a new inhibitor against a novel target. Each strategy has the potential to improve treatment of head and neck cancer, which individuals with FA are susceptible to developing.