Mechanisms of the Antitumor Activity of Low Molecular Weight Heparins in Pancreatic Adenocarcinomas

Abstract

Immune checkpoint inhibitors have revolutionized cancer treatment in the last decade. Despite the progress in immunotherapy, most pancreatic cancer patients still do not derive benefit when receiving immune-based therapies. Recently, resistance mechanisms to immune therapies have been mainly focused on tumor microenvironment properties. Pancreatic cancer is considered one of the most lethal and difficult to treat tumors due to its highly immunosuppressive and desmoplastic microenvironment. Low molecular weight heparins (LMWHs) have been used for the treatment and prevention of thromboembolic disease in these patients. However, many nonanticoagulant properties attributed to LMWHs have been described. Exploiting LMWH properties in a combined treatment modality with immune checkpoint inhibition and chemotherapy could provide a new approach in the management of pancreatic adenocarcinoma patients. The ability of LMWH to interfere with various aspects of the tumor microenvironment could result in both the alleviation of immunosuppression and improvement in drug delivery within the tumor, leading to higher cancer cell destruction rates and more potent immune system activity that would, ultimately, lead to better patient outcomes.