SapC-DOPS – a Phosphatidylserine-targeted Nanovesicle for selective Cancer therapy

• Main Authors: Kombo F. N’Guessan, Priyankaben H. Patel, Xiaoyang Qi
• Format: Article
• Language: English
• Published: BMC 2020-01-01
• Series: Cell Communication and Signaling
• Subjects: Phosphatidylserine; SapC-DOPS; Flippase; Pancreatic cancer; Lung cancer; Brain tumor
• Online Access: https://doi.org/10.1186/s12964-019-0476-6

Abstract Phosphatidylserine (PS) is normally located in the inner leaflet of the membrane bilayer of healthy cells, however it is expressed at high levels on the surface of cancer cells. This has allowed for the development of selective therapeutic agents against cancer cells (without affecting healthy cells). SapC-DOPS is a PS-targeting nanovesicle which effectively targets and kills several cancer types including pancreatic, lung, brain, and pediatric tumors. Our studies have demonstrated that SapC-DOPS selectively induces apoptotic cell death in malignant and metastatic cells, whereas untransformed cells remain unaffected due to low surface PS expression. Furthermore, SapC-DOPS can be used in combination with standard therapies such as irradiation and chemotherapeutic drugs to significantly enhance the antitumor efficacy of these treatments. While the PS-targeting nanovesicles are a promising selective therapeutic option for the treatment of cancers, more preclinical studies are needed to fully understand the mechanisms leading to non-apoptotic PS expression on the surface of viable cancer cells and to determine the effectiveness of SapC-DOPS in advanced metastatic disease. In addition, the completion of clinical studies will determine therapeutic effects and drug safety in patients. A phase I clinical trial using SapC-DOPS has been completed on patients with solid tumors and has demonstrated compelling patient outcomes with a strong safety profile. Results from this study are informing future studies with SapC-DOPS. Abstract video Graphical abstract