Excessive toxicity from chemotherapy and radiation makes treatment for SCC in FA quite challenging and leads to dismal outcomes, in fact fatal outcomes in most patients. Thus, there is clearly a need for a new approach both for prevention and/or treatment that has fewer and less severe side effects. Our previous study showed that a naturally occurring antioxidant Quercetin, is safe and well tolerated in pre-HCT patients with FA. In this study we propose to utilize Quercetin to prevent development of SCC in post-transplant FA patients. We expect this approach to work, as Quercetin has been reported to lead to prevention of SCC in mice (non-FA). In our hands, Quercetin decreases tumor growth in FA head and neck cancer cell lines, by killing the tumor cells. In our previous study, we see evidence of decreased DNA damage in oral mucosa brushings from patients with FA (pre-HCT) after treatment with quercetin for one month. Based on these strong and promising data we propose a pilot study of Quercetin treatment for 6 months at least (with an option of up to total of 2 years) in 20 post-transplant patients with FA. Our clinical and laboratory tests will confirm the beneficial effect of quercetin (e.g. decreased oxidative stress-in blood and saliva, along with decrease in ongoing DNA damage in buccal mucosa compared to baseline). Expected positive impact is that success will lead to a new prevention strategy for SCC in post-HCT patients with FA that will eliminate or at least delay the development of SCC. This is an innovative approach in our opinion, as Quercetin acts on all of the pathways implicated in SCC development in FA, i.e. oxidative stress, NF kappa B, and aldehyde mediated tumor growth. This study will confirm a simple and feasible approach for the prevention of SCC with use of oral quercetin.
Researchers: Parinda Mehta