Abstract 2501: Differential protein signatures in cancer cell lines after dosing with anticancer molecules in vitro and in vivo.

Abstract

Abstract Using a sensitive proteomics platform that can precisely and simultaneously measure 1129 distinct proteins (SOMAscan™), we profiled the proteomic changes in cancer cell lines and xenograft models following exposure to several oncological agents. Our goals were to identify novel biomarkers and drug targets, and to map out pharmacological MOA, with the ultimate goal of assessing the translatability of in vitro and preclinical models to human patients. We have generated multiple successful examples of using our platform in this manner. We treated a breast cancer cell line MCF-7 with eight pharmacological agents, including TamoxifenTM and TaxolTM. We have assessed PKC-δ resistant and sensitive lung cancer cell lines with a PKC-δ inhibitor, and profiled protein changes in response to these compounds. To assess how well in vitro models translate to preclinical models, we profiled protein changes in HCC827 (sensitive) or H1299 (resistant) cell lines treated with erlotinib (TarcevaTM), and NOD/SCID mice implanted with HCC827 cells and dosed with erlotinib. We observed good concordance of the protein changes in the HCC827 cell-lines and the xenograft models, which included cyclin A and p27KIP1 expression levels (proteins previously associated with erlotinib sensitivity) as well as additional protein changes with highly plausible connections to erlotinib's mode of action. These newly identified proteins may have implications for treating patients that develop resistance to erlotinib in the clinic, and suggest new targets for drug development. A human clinical study is underway to explore how the proteomic changes seen in this study translate to erlotinib treatment of NSCLC patients in the clinic. Citation Format: Robert Swift, Deb Ayers, Ying Chang, Darryl Perry, Sheri Routt, Sheri Wilcox, Bridget Lollo, Nick Saccomano. Differential protein signatures in cancer cell lines after dosing with anticancer molecules in vitro and in vivo. [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 2501. doi:10.1158/1538-7445.AM2013-2501 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.