we hypothesized that in the mutant K ras cell lines activation of the downstream pathways by Ras could be in charge of their observed resistance to lapatinib mediated radiosensitization. Downstream signaling from EGFR/HER2 and Ras are both known to trigger many important pathways in keeping, such as the PI3K/Akt price Ibrutinib pathways and Raf/MEK/ERK. To decide whether inhibition of Raf/MEK/ERK and/or PI3K/Akt could radiosensitize pancreatic cancer cells, we evaluated the ability of U0126, a MEK inhibitor and identified breast cancer radiosensitizer, and LY294002, a PI3K inhibitor, to sensitize our panel of pancreatic cancer cell lines to radiation induced cell death. Despite effective inhibition of ERK1/2 phosphorylation in all cell lines by U0126, this inhibition of MEK/ERK activation didn’t radiosensitize some of the pancreatic cancer cell lines. A modest increase in Akt activation was seen in some cell lines in response to U0126 treatment, an outcome consistent with feedback signaling circles defined by others and consistent with the purpose of Akt in the radiation response. In comparison, therapy with LY294002 resulted in successful inhibition of Akt with major radiosensitization of most cells regardless Metastatic carcinoma in their K ras mutational status. . Nelfinavir blocks Akt phosphorylation and radiosensitizes both wild-type and mutant E ras cell lines Several FDA-APPROVED HIV protease inhibitors including nelfinavir and ritonivir have been demonstrated to block Akt signaling and radiosensitize HNSCC, breast, lung, and brain cyst cell lines. Because presently available PI3K inhibitors have proven unacceptable supplier Cilengitide scientific poisoning, we sought to gauge whether inhibition of the PI3K/Akt process with nelfinavir would radiosensitize pancreatic cancer cells. . Cells treated using a technically possible measure of nelfinavir or vehicle alone showed decreased Akt initial after 28 hours, although not after a four-hour exposure. Little change in ERK1/2 activation or cell cycle distribution was seen at either time point. To ascertain the result of nelfinavir on radiation response, cells were likewise pre-treated with nelfinavir for either 2 or 26 hours before and 2 hours after irradiation and their power to 7 proliferate in clonogenic survival assays decided. Both mutant and wild-type E ras cells were radiosensitized after 26 hours of nelfinavir pre-treatment. Consistent with results on Akt initial, no radiosensitization was seen after 2 hour pre-treatment. To exclude the chance that nelfinavir treatment induces growth arrest, MTS assay was used to check proliferation after exposure to nelfinavir for either 2 or 26 hours. No factor in growth was seen with either amount of exposure in any of the four cell lines tested.