Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2021; 13(6): 550-559
Published online Jun 15, 2021. doi: 10.4251/wjgo.v13.i6.550
Targeting of elevated cell surface phosphatidylserine with saposin C-dioleoylphosphatidylserine nanodrug as individual or combination therapy for pancreatic cancer
Harold W Davis, Ahmet Kaynak, Subrahmanya D Vallabhapurapu, Xiaoyang Qi
Harold W Davis, Ahmet Kaynak, Subrahmanya D Vallabhapurapu, Xiaoyang Qi, Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Brain Tumor Center at UC Neuroscience Institute, Cincinnati, OH 45267, United States
Ahmet Kaynak, Xiaoyang Qi, Department of Biomedical Engineering, College of Engineering and Applied Science, University of Cincinnati, Cincinnati, OH 45221, United States
Author contributions: Davis HW and Qi X conceptualized the review; Kaynak A helped generate the figures; all authors made major contributions to the review’s literature search and contributed to drafting the manuscript; all authors contributed to some or all of our laboratory’s original studies discussed in this review; all authors provided critical review and approved the final manuscript before submission.
Supported by Pancreatic Cancer Action Network Translational Research Grant, No. 20-65-QIXI; Give Hope Foundation, National Institutes of Health, No. R01CA158372 and No. R21NS095047; and CCTST Pilot Collaborative Studies, Bearcats Against Cancer, and Hematology-Oncology Programmatic Support from University of Cincinnati College of Medicine (to Qi X).
Conflict-of-interest statement: Qi X is listed as an inventor on the patent for SapC-DOPS technology that is the subject of this review. Consistent with current Cincinnati Children’s Hospital Medical Center policies, the development and commercialization of this technology has been licensed to Bexion Pharmaceuticals, LLC, in which Qi X, holds a minor (< 3%) equity interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Xiaoyang Qi, PhD, Professor, Division of Hematology/Oncology, Department of Internal Medicine, University of Cincinnati College of Medicine, Brain Tumor Center at UC Neuroscience Institute, 3512 Eden Avenue, Cincinnati, OH 45267, United States.
Received: January 29, 2021
Peer-review started: January 29, 2021
First decision: April 6, 2021
Revised: April 13, 2021
Accepted: May 10, 2021
Article in press: May 10, 2021
Published online: June 15, 2021

Pancreatic cancer is one of the deadliest of cancers with a five-year survival of roughly 8%. Current therapies are: surgery, radiation and chemotherapy. Surgery is curative only if the cancer is caught very early, which is rare, and the latter two modalities are only marginally effective and have significant side effects. We have developed a nanosome comprised of the lysosomal protein, saposin C (SapC) and the acidic phospholipid, dioleoylphosphatidylserine (DOPS). In the acidic tumor microenvironment, this molecule, SapC-DOPS, targets the phosphatidylserine cancer-biomarker which is predominantly elevated on the surface of cancer cells. Importantly, SapC-DOPS can selectively target pancreatic tumors and metastases. Furthermore, SapC-DOPS has exhibited an impressive safety profile with only a few minor side effects in both preclinical experiments and in phase I clinical trials. With the dismal outcomes for pancreatic cancer there is an urgent need for better treatments and SapC-DOPS is a good candidate for addition to the oncologist’s toolbox.

Keywords: Pancreatic cancer, Saposin C, Dioleoylphosphatidylserine, Phosphatidylserine-targeted therapy, Chemotherapy, Radiation

Core Tip: This review presents the mechanisms and efficacy of saposin C-dioleoylphosphatidylserine (SapC-DOPS), a novel phosphatidylserine (PS) biomarker-targeted nanodrug, alone and in combination with other treatment modalities for the treatment of pancreatic ductal adenocarcinoma (PDAC) tumors. Our results indicate that SapC-DOPS preferentially targets cells with high surface PS which are primarily in the G2/M phase of the cell cycle. Other treatment modalities such as Gemcitabine, Abraxane and radiation target G1 phase cells that have low surface PS. Combination of SapC-DOPS and Gemcitabine/Abraxane or radiation significantly inhibits tumor growth of orthotopic PDAC tumors in vivo and increases survival compared to individual treatments.