ANTIPARASITIC DRUG IVERMECTIN EXHIBITS ANTITUMOR ACTIVITY IN PANCREATIC DUCTAL ADENOCARCINOMA MODELS

GONZALEZ MORAN FLORENCIA; SOLERNO LUISINA; LLAVONA CANDELA; FARINA HERNAN; DUSETTI NELSON; IOVANNA JUAN; SEGATORI VALERIA; GARONA JUAN; ALONSO, DANIEL F.; GOTTARDO MF

Congreso; VI International Congress in Translational; 2023

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related deaths worldwide. In addition, its 5-year survival rate is less than 5% due to late diagnosis and limited treatment options. Ivermectin (IVM) is a widely used antiparasitic drug that has been repositioned as an antitumor agent given its capacity to reverse multidrug resistance, inhibit proliferation and decrease mitochondrial biogenesis. The aim of the present preclinical study was to investigate the antitumor effects of IVM in pancreatic ductal adenocarcinoma. Using TCGA GTEX databases and the UCSC Xena and GEPIA2 platforms (PAAD/n=179), we explored putative molecular targets associated with IVM reported anti-cancer mechanisms, confirming their overexpression in PDAC versus normal tissue, and its direct correlation with worse clinical outcomes. We further assessed the correlation of such targets with different clinically-relevant tumor immune infiltrates using the Tumor Immune Estimation Resource (TIMER2.0) platform. Interestingly, we found a strong positive association between their expression and infiltration levels of cancer-associated fibroblasts as well as myeloid-derived suppressor cells in PDAC clinical samples (p