Polymeric Chloroquine as an Effective Antimigration Agent in the Treatment of Pancreatic Cancer

Abstract

Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent.

Targeting KRAS in Pancreatic Ductal Adenocarcinoma: The Long Road to Cure

“…To better target autophagy, different technologies have been applied to CQ and HCQ. Chloroquine-loaded nanoparticles and polymeric HCQ (a macromolecular multivalent version thereof) have been explored with promising data [158,159]. In addition to them, many other autophagy inhibitors targeting lysosomes are in clinical development, such as the Lys05 family, GNS561 (Genoscience Pharma, Marseille, France), and ROC-305 [160].…”