Abstract
Abstract Purpose: The human papilloma virus (HPV) has recently become a prevalent cause of human head and neck cancer (HNC), which often exhibits dysregulated epidermal growth factor receptor (EGFR) signaling. We previously reported that in non-HPV-associated HNC, inhibition of EGFR (EGFRi) attenuates DNA double stranded break (DSB) repair and subsequently sensitizes tumors to inhibitors of poly (ADP-ribose) polymerase (PARP), which target DNA repair deficient tumors. Because patients with HPV-associated HNC have been shown to exhibit increased sensitivity to DNA damage, we evaluated the response of HPV (+) HNC cells to combination EGFRi and PARPi compared to HPV (-) HNC cells. Methods: HPV (-) UM-SCC1 and UM-SCC6, as well as HPV (+) SCC-47 and SCC-90 were utilized for in vitro studies. Cell growth and survival fraction were evaluated via cell proliferation and colony formation assays, respectively. DNA damage studies were performed using standard γ-H2AX and Rad51 foci. Lastly, in vivo studies were conducted in mice bearing HNC tumor xenografts as well as a human tumor explant from a lymph node metastasis of a HPV(+) HNC patient. Results: Interestingly, HPV (+) HNCs exhibited the greatest sensitivity both in vitro and in vivo to PARP inhibition alone. This correlated with a blunted DNA damage response. In contrast, HPV (-) HNCs were most sensitive to combination EGFRi/PARPi, which correlated with persistent DNA damage. Conclusions: HPV(+) head and neck cancers may be sensitive to PARP inhibition alone. Our in vitro and in vivo results warrant further testing of PARP inhibitors as part of therapy for HNCs. Citation Format: Tiffiny Cooper, Marcela Rodriguez, Hoa Q. Trummell, Alice Weaver, James A. Bonner, Eddy S. Yang. PARP inhibition in HPV positive head and neck cancers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 635. doi:10.1158/1538-7445.AM2013-635
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