Receptor proteins were precipitated from cell lysates with a commercial antibody against HER2 or with a non commercial antibody against HER1/EGFR. Lapatinib blocks EGFR and HER2 activation We have enzalutamide shown previously that both lapatinib and erlotinib, an EGFR selective tyrosine kinase inhibitor, block the growth agar soft of several pancreatic cancer cell lines1. . Because EGFR 5 inhibition is demonstrated to radiosensitize other cancers, including head and neck squamous cell carcinomas and breast cancer, we sought to find out whether these compounds may also radiosensitize pancreatic cancer cells and whether this radiosensitization correlated with EGFR and HER2 expression. We first evaluated by qRT PCR the relative expression degrees of all four members of the family of receptors among a panel of four pancreatic cancer cell lines. EGFR levels were 10 17 fold greater in the PANC 1 and T3M4 cells in accordance with that observed in the Capan 2 and MIA PaCa 2 cells, while HER2 levels were similar among all four lines. Phrase of HER3, a member of family that lacks kinase activity, was approximately 10 fold greater within the Capan 2 and T3M4 cells. HER4, the ultimate relative, had very-low mRNA expression levels across all cell lines. An anti proliferative effect was shown by all cell lines in response to increasing concentrations of both erlotinib and lapatinib. The dual EGFR/HER2 phytomorphology inhibitor lapatinib demonstrated improved growth inhibitory activity compared to erlotinib in 2 and MIA PaCa 2 cell lines, a finding consistent with low levels of EGFR mRNA in these cell lines. PANC 1 and T3M4 cells had higher levels of EGFR than HER2 expression, and demonstrated comparable growth inhibition by lapatinib and erlotinib. To show that lapatinib blocks ligand triggered EGFR and HER2 activation in our pancreatic cells activation of receptors was analyzed by immunoprecipitation followed by western blot analysis. In line with what we pifithrin a and others have previously reported using in vitro, in vivo, and individual samples and reviewed in, lapatinib blocked activation of both EGFR and HER2 in every four pancreatic cell lines. . Pancreatic cancer cell lines harboring E ras mutations are resistant to lapatinib mediated radiosensitization As a result of improved anti-proliferative and ligand triggered receptor inhibition of lapatinib in the tested cell lines, we chose to investigate whether lapatinib can radiosensitize pancreatic cancer cells. Clonogenic success assays were performed on our section of cells that were both treated with lapatinib or vehicle alone for your 2 hours preceding and 2 hours after irradiation. We chose this short duration of drug treatment since the clonogenic survival and cell cycle distribution of non irradiated cell lines that were pretreated in this style with either lapatinib or DMSO control weren’t statistically different, suggesting that the 4 hour exposure to lapatinib did not radiosensitize cells simply by inhibiting proliferation or by redistributing cells into a more radiosensitive cycle of the cell cycle.