Abstract LB-429: Dormant cancer cells contribute to residual disease in a mouse model for reversible pancreatic cancer

Abstract

Abstract The initiation and progression of premalignant lesions into pancreatic ductal adenocarcinomas (PDACs) is governed by a series of genetic changes, but it is still unknown whether these alterations are still required for the maintenance of primary and metastatic PDAC. Here we show that the c-Myc oncogene is upregulated throughout the entire process of neoplastic progression in human PDAC. To address whether this oncogene is essential for the growth and survival of cancer cells, we developed a novel mouse model that allows a temporally and spatially controlled expression of c-Myc in pancreatic progenitors and derived lineages of the exocrine pancreas. Upregulation of c-Myc is sufficient to cause adenocarcinomas after a short latency, and haploinsufficiency in Cdkn2a dramatically increases the rate of metastasis. Despite a macroscopically complete regression of primary, metastatic, and transplantable tumors following the downregulation of c-Myc, some cancer cells remain dormant. A significant number of these residual neoplastic cells express cancer stem cell markers, and re-expression of exogenous c-Myc leads to rapid cancer recurrence. Collectively, the results of this study suggest that c-Myc plays a significant role in the progression and maintenance of PDAC, but additional therapeutic strategies are necessary to eradicate residual cancer cells to prevent cancer relapse. 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 LB-429. doi:1538-7445.AM2012-LB-429