Abstract 1323: Novel autophagy inhibitor to treat pancreatic cancer

In this study, we develop a novel autophagy inhibitor targeting one of the most aggressive cell populations present in pancreatic tumors, the pancreatic cancer stem cell (CSC). Targeting this population which has the malignant properties of tumorigenesis/tumor recurrence, the ability to differentiate into a heterogenous tumor cell types and can self-renew is a new strategy to alleviate the current dismal 10% five-year survival rate of pancreatic cancer. Here we characterize an autophagy inhibitor which is a first-in-class nanoparticle comprised of a chloroquine-derived small molecule drug that can self-assemble into a micelle. Due to its favorable pharmacokinetic properties and the CSC reliance on autophagy, our compound is able to selectively target this cell population both in vitro and in vivo. Additionally, the compound has shown synergy with the current standard of care chemotherapeutic, gemcitabine, with an 88.9% reduction in tumor volume in the combination of the two drugs compared to gemcitabine treated alone (p Citation Format: Mythili Ramachandran, Zhao Ma, Yuanpei Li. Novel autophagy inhibitor to treat pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1323.