Abstract 2819: Targeting inflammation and pancreatitis blocks tumor-initiating stem cells and pancreatic cancer progression

Pancreatic cancer (PC) is a deadly disease with the lowest survival of all cancers. Recent development of genetically engineered mouse models (GEMs) for PC that recapitulate human disease progression has enabled development of new strategies to delay or inhibit pancreatic cancer and testing of experimental interventions in preclinical trials. Pancreatic tumor-initiating or cancer stem cell (CSC) populations contribute to tumor growth, metastasis, and resistance to therapy. We first found that expression of the CSC marker DclK1 occurs at an early stage of PC in both early and late pancreatic intraepithelial neoplasia (PanINs) and increases as the disease progresses. Genome-wide next generation sequencing of pancreatic ductal adenocarcinoma (PDAC) from GEMs revealed significantly increased DclK1 along with inflammatory genes. Genetic ablation of cyclo-oxygenase (COX)-2 decreased the DclK1 in GEMs. Induction of inflammation with cerulein induced pancreatitis in GEMs increased DclK1, and Dclk1 was reduced by the novel anti-inflammatory dual COX/5-lipoxygenase (5-LOX) inhibitor licofelone. We investigated the long term pharmacologic inhibitory efficacy of licofelone on PDAC in vivo using a GEM model. GEM (n = 86) and wild type mice (n = 24) were fed a diet containing different doses of licofelone for 300 days and evaluated for formation of PanINs and for their progression to PDAC. Dietary licofelone at tested doses significantly inhibited the incidence of PDAC (60-90%; p

Source: Cancer Research - August 2, 2015 Category: Cancer & Oncology Authors: Mohammed, A., Janakiram, N. B., Madka, V., Brewer, M., Ritchie, R. L., Lightfoot, S., Kumar, G., Sadeghi, M., Patlolla, J. M. R., Yamada, H., Cruz-Monserrate, Z., Houchen, C. W., Steele, V. E., Rao, C. V. Tags: Prevention Research Source Type: research