Abstract PO-043: Interception of pancreatic cancer progression

Abstract

Pancreatic Cancer (PC) is projected to be one of the leading causes of cancer related death by 2030. Although other cancers have made significant strides towards improved treatment, PC still remains at a 9% fiver year survival rate due to end-stage diagnosis, aggressive metastasis, and a protective stromal wall. Therefore, to identify novel therapeutic targets, our lab focuses on studying cancer stem cells, a highly chemo-resistant sub-population of pancreatic cancer cells. RNA-seq analysis of these cancer stem cells has revealed a number of genes that are enriched compared to non-therapy resistant cells and normal pancreas. We hypothesize that genes turned on through pancreatic cancer progression contribute to therapy resistance. If PC could be targeted at earlier stages, it would be possible for therapeutics to bypass the wealth of issues that occur as it advances. By cross referencing our RNA-seq analysis to sequencing performed at various stages of pancreatic cancer development in mice, a subset of genes is not only up-regulated in therapy resistant cells, but increases in expression as normal pancreas progresses to an end stage tumor. Preliminary studies have shown that inhibition of these select genes reduces growth of mouse pancreatic cancer in vitro and in vivo. Ongoing studies are to (1) test if inhibition of these genes reduces early stage PC growth in vitro and in vivo, and (2) test how gene knockdown affects human pancreatic cancer cell growth in vitro and in vivo. Citation Format: Matthew L. McDermott, Lesley P. Ferguson, Kendall Chambers, Nirakar Rajbhandari, Tannishtha Reya. Interception of pancreatic cancer progression [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-043.