Fanconi anemia patients are dramatically predisposed to early-onset and aggressive head, neck, and anogenital squamous cell carcinoma (SCC). Treating Fanconi SCCs is challenging due to high-frequency recurrence and patient chemosensitivity, yielding an average survival rate of <2 years post-diagnosis. New treatment strategies are desperately needed. We want to tackle this problem by identifying ways to kill cancer cells but spare the other cells in FA patients. We will build cell lines that mimic patient cancers and use them to identify their vulnerabilities (“Achilles heel”) which would lead to development of better therapeutics.