When along with radiation in breast cancer cells ABT 888 has also been noted to cause senescence. Furthermore, other PARPi can stimulate G2/M accumulation of cells. Hence, as yet another potential mechanism of improved cytotoxicity, cell cycle distribution subsequent ABT CTEP 888 and mix C225 to evaluate cell cycle changes was conducted in UM SCC1 cells. As shown in Fig. 7C, no cell cycle redistribution was seen. These results demonstrated that the following enhanced cytotoxicity with ABT 888 and C225 induced attenuation of DSB repair pathways weren’t because of cell cycle effects. Discussion In this study, we show that C225, an inhibitor of EGFR, increases cellular susceptibility for the PARPi ABT 888 in head and neck cancer cells. The process of enhanced cytotoxicity involved C225 mediated attenuation of the two key DNA DSB fix pathways, NHEJ and HR, leading to the persistence of DNA damage following PARPi and the subsequent activation of the intrinsic pathway of apoptosis. This combination of ABT and C225 888 could be especially fascinating for programs that include Endosymbiotic theory other DNA damaging agents including radiation. The EGFR has been implicated in numerous cellular processes, including cell proliferation and survival, angiogenesis, and DNA damage response and repair. Specifically, with regards to DNA damage response, EGFR has been proven to translocate to the nucleus and interact with DNA Pk to stimulate NHEJ. Activated EGFR can also improve Rad51 foci and expression levels to manage HR. These actions by EGFR have already been attributed to weight of EGFR amplified/mutated c-Met inhibitor cancers to DNA damaging agents and provide basis for targeted inhibition of EGFR. To get a job of EGFR in the DNA damage and repair pathways, C225, which stops EGFR, attenuates the 2 main DNA DSB repair pathways, HR and NHEJ, by altering Rad51 and DNA Pk foci levels, respectively. C225 also inhibited DNA Pk phosphorylation. Those things of C225 on HR mediated fix provide rationale for why the novel mixture of C225 and PARPi increases cytotoxicity in head and neck cancer cells, as PARPi is demonstrated to target HR deficient cells. Also, PARP inhibited cells have been shown to be sensitized to inhibitors of the NHEJ pathway, indicating that NHEJ can also be a pathway of unsure SSBs. This may also explain the cytotoxicity observed in PARPi and C225 treated cells. Furthermore, as C225 triggers equally a NHEJ and HR repair deficit, the combination of C225 with PARPi contributes to a higher percentage of treated cells with chronic DSBs. Given these findings, cells subjected to C225 and PARPi must be exquisitely prone to other DNA damaging agents, such as for instance light. That is a location of active study in our laboratory.