Current management of pancreatic cancer is mired by late presentation and lack of effective adjuvant therapy. We investigated the genome-wide expression profiles of pancreatic cancer cell lines, AsPC-1 and BxPC-3, to identify diagnostic markers and therapeutic targets for this disease.Cells were treated with Camptothecin (pro-apoptotic) or phorbol 12-myristate 13-acetate (PMA - pro-inflammatory). Non-treated cells were used as control. RNA was extracted and hybridised to Affymetrix arrays. Differentially expressed genes were identified using ArrayAssist®. Significantly interacting genes were linked and pathways mapped using Pathway Studio®. Genes were selected for validation by qRT-PCR based on pathway significance and fold change.Genesets for each condition displayed a 1.5 fold differential expression with p values <0.02. Pathway analysis revealed that camptothecin was primarily involved in signal transduction via MAP kinase pathways. PMA induced apoptotic signalling through a family of receptors known collectively as 'death receptors' including Fas, DR3 and DR4-5. Quantitative RT-PCR confirmed microarray expression profiles. Genes selected included those already implicated in pancreatic cancer (SMAD3, BRCA2, MMP-1, IL1-R1) and also several not previously reported. Although camptothecin and PMA had distinct expression profiles, 3 genes (ATF3, PLAU and SOD2) were ≥ 10 fold up- and down-regulated in AsPC-1 and BxPC-3, respectively. In conclusion, novel genes have been identified in pancreatic cancer for evaluation as screening and therapeutic targets. Three genes (ATF3, PLAU and SOD2) are involved in early stage invasion and cell dissociation, thus demonstrating potential as specific tumour markers or molecular targets in pancreatic cancer.