PARP Inhibition To Enhance Induction for Head and Neck Cancer

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DESCRIPTION (provided by applicant): Induction (neoadjuvant) chemotherapy for locally advanced head and neck cancer (LAHNC) constitutes a three drug regimen consisting of a taxane, a platin, and 5-fluorouracil (TPF). TPF induction chemotherapy is effective but is associated with significant toxicity especially myelosuppression and mucositis. Overall response rates exceeding 80% and complete response (CR) rates ranging from 20 to 54% have been reported. Achieving CR correlates with good prognosis while failure to respond to induction chemotherapy predicts resistance to subsequent radiotherapy. Toward enhancing CR rates after induction therapy in LAHNC, we have initiated a trial combining the poly(ADP-ribose) polymerase inhibitor veliparib with cisplatin, 5FU and docetaxel therapy. Previously, we have shown that veliparib enhances accelerated senescence in cells and tumors treated with radiation or genotoxic therapy. Here, we intend to pursue parallel preclinical research constituting correlative studies for this trial. Thus, we intend to examine tissue culture, animal models and biopsies from treated patient tumors to understand whether accelerated senescence is a potential mediator of success in induction therapy, with or without veliparib. We also hope to identify biomarkers that indicate sensitivity to veliparib and/or induction therapy, and that indicate success of these treatments.