The therapeutic agent SapC-DOPS could be used for treatment of lung cancer, according to a new study using animal models and human tissue culture that was published in Molecular Cancer Therapeutics (2015; doi:10.1158/1535-7163.MCT-14-0661).
Lung cancer is the most common and the deadliest type of cancer worldwide, with about 221,000 new cases and an estimated 158,000 deaths in 2015 in the United States, according to the American Cancer Society.
Xiaoyang Qi, PhD, associate director and associate professor in the Division of Hematology Oncology at the University of Cincinnati (UC) College of Medicine in Ohio and a member of the Cincinnati Cancer Center, the UC Cancer and Neuroscience Institutes and the Brain Tumor Center, said these findings indicate that SapC-DOPS shows promise for treatment of one of the deadliest cancers globally. The findings also provide stronger evidence that this agent could be a key treatment for a variety of cancers.
“I partnered with scientists at Nanjing Medical University in China for this research, as lung cancer in China is a major health issue,” Qi said. “As reported by the International Agency for Research on Cancer, more than half of lung cancer deaths caused by air pollutants worldwide occurred in China and other East Asian countries.
“Standard treatment options for lung cancer, including chemotherapy, radiation, and surgery, have undesirable side effects that impact the quality of life of the cancer patient, which is why the targeted use of SapC-DOPS could be so beneficial.”
SapC-DOPS consists of a lysosomal protein, saposin C (SapC), and a phospholipid named dioleoylphosphatidylserine (DOPS), which are combined and assembled into tiny cavities, or nanovesicles, to target and kill various forms of cancer cells.
Qi and collaborators have previously found that combining these two natural cellular components (SapC-DOPS) caused cell death in many cancer cell types including brain, skin, prostate, blood, breast, and pancreatic cancer, while sparing normal cells and tissues.
“Liposomal formulations as vehicles for drug delivery are the subject of intense research,” he continued. “Compared with non-encapsulated, free drugs, they provide improved biocompatibility and targeted delivery.”
Qi explained that, despite promising results in preclinical models of lung cancer and many other cancer types, only a few nontargeted liposomal formulations have been approved for cancer treatment by regulatory agencies. He said that clinical trials are under way to evaluate some of these in lung cancer patients, but, so far, these liposomes have been shown to be less effective when compared with free drug administration. He stated that this is why the SapC-DOPS research is promising as a targeted treatment for lung cancer.
In this study, researchers used SapC-DOPS to selectively target the cell membrane of lung tumors in animal models and in human cell cultures.
“We observed that the nanovesicles selectively killed human lung cancer cells, and the noncancerous, or untransformed cells, remained unaffected,” Qi said. “This toxic effect correlated to the surface exposure level of phosphatidylserine on the tumor cells.”
Importantly, animals treated with SapC-DOPS showed clear survival benefits and their tumors shrank or disappeared.
“Our results show that SapC-DOPS could be a promising treatment option for lung cancer worthy of further clinical study.”