Targeting of elevated cell surface phosphatidylserine with saposin C-dioleoylphosphatidylserine nanodrug as individual or combination therapy for pancreatic cancer

摘要

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.