315PInhibition of JAK1 sensitizes human head and neck cancer cells to cetuximab.

Background Cetuximab (an inhibitor of EGFR) is commonly utilized for the treatment of head and neck cancers. It has been employed in combination with radiation or multi-agent chemotherapy for locoregionally advanced and metastatic head and neck cancer respectively. This study explored the use of cetuximab plus an JAK1 inhibitor (JAK1i), which is a protein that is downstream in EGFR signaling, in order to test whether this dual inhibition could accentuate the effects of cetuximab. Methods Human head and neck squamous cell cancer cells (UM-SCC-6 cells) were cultured as previously described (Bonner JA et al. BMC Cancer 15:673). The JAK1 inhibitor (JAK1i) was obtained from Calbiochem, LaJolla, CA. Standard assays of immunoblots, proliferation, apoptosis and comet assays were utilized (Bonner JA et al. BMC Cancer 15:673). Results The combination of cetuximab (0.5 μg/ml) and JAK1i (1µM) resulted in greater inhibition of STAT-3 than either agent alone on immunoblot analysis. Likewise, the combination treatment resulted in greater inhibition of cell proliferation (at 72 hours), greater apoptosis and enhanced DNA double strand breaks (comet) compared to either agent given alone. Conclusions Cetuximab initially showed activity in head and neck cancer over 20 years ago. It is currently used in combination with radiation or chemotherapy for these patients. The results reported herein suggest that the anti-proliferative effects of cetuximab can be enhanced with the addition of JAK1 inhibition. Further work exploring the targeting of various steps in EGFR signaling is warranted in head and neck cancer. Legal entity responsible for the study James A. Bonner. Funding Has not received any funding. Disclosure J.A. Bonner: Honoraria (institution), Advisory / Consultancy: Bristol-Myers Squibb Company; Honoraria (institution), Advisory / Consultancy: Eli Lily and Company; Honoraria (institution), Advisory / Consultancy: Merck Serono; Honoraria (institution), Advisory / Consultancy: Cel-Sci. E. Yang: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Eli Lilly. All other authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]