Abstract 3697: Phase II study of therapy selected by molecular profiling in patients with previously treated metastatic pancreatic cancer - SU2C-001

Abstract

Abstract We have completed a second line Phase II study of therapy to be selected by molecular profiling in 35 patients with previously treated metastatic pancreatic cancer. On this study all patients have a biopsy of a metastatic lesion (usually liver). Therapeutic targets are identified by profiling the metastatic biopsies with the combined use of immunohistochemistry (IHC), comparative genomic hybridization (CGH) on sorted tumor populations, and correlating gene expression microarray data to that of a panel of xenografts for which drug sensitivity has been previously determined. The IHC assays are performed in a CLIA certified laboratory and include the following therapeutic targets: MRP1, TOPO1, MGMT, PGP, Her2/Neu, PTEN, c-kit, RRM1, EGFR, BCRP, PDGFR, TOP2A, TS, ERCC1, SPARC, ER, PR, and AR. In addition each sample is screened by PCR for the presence of the most common K-RAS mutations. Gene expression microarray analysis is performed at John Hopkins University using Affymetrix U133 Plus 2.0 gene arrays. For CGH analysis flow sorted nuclei of diploid and aneuploid tumor cell populations are processed and hybridized to 400,000 feature CGH arrays. We have identified distinct high level focal amplicons targeting AKT2, LYN, RET, CDK6, K-RAS, MYCBP, BCL11A, RASA1 and WNT6, and gene specific homozygous deletions including CDKN2A, PTEN, MAP2K4, RASA1 and PARK2 in the sorted aneuploid tumor nuclei. In an effort to elucidate new targets and potential contexts of vulnerability based on the results of this trial, we have extracted combined gene level data for each patient and present these mapped to 32 pancreatic specific pathways and processes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3697. doi:1538-7445.AM2012-3697