Published online Jun 15, 2021. doi: 10.4251/wjgo.v13.i6.550
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.
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.