Researchers at Oregon State University have developed a technique for simultaneously treating lung cancer and a serious muscle-wasting condition that often accompanies it.
The study, published in the Journal of Controlled Release, involves lipid nanoparticles delivering therapeutic genetic material to lung tumors.
In a mouse model, scientists led by Oleh Taraula and Yoon Tae Goo of the OSU College of Pharmacy showed that a type of nanocarrier loaded with follistatin messenger RNA is able to accumulate in tumors. Once there, the mRNA triggers cells to produce the follistatin protein, which plays a key role both in inhibiting tumors and promoting muscle tissue growth.
The lipid nanoparticles, or LNPs, can be administered intravenously and reach the lungs courtesy of another protein, vitronectin, that's found in blood serum. Lipids are fatty acids and similar organic compounds including many natural oils and waxes. Nanoparticles are tiny pieces of material ranging in size from one- to 100-billionths of a meter.
"We found that these LNPs bind vitronectin in the bloodstream, which then directs them to lung cancer tumors by interacting with integrin receptors that are overexpressed on the tumor surface," Taratula said.
Integrin receptors are like bridges and that regulate how cells respond to their surrounding environment.
"Systemic delivery of mRNA therapeutics to lung cancer tumors has been a significant challenge in our field, and this work offers a promising solution," Taratula said. "Compared to conventional LNPs, which tend to accumulate in the liver upon systemic administration, our approach achieved an approximately 2.5-fold greater reduction in tumor burden."
Lung cancer is the third most common cancer in the United States and the leading cause of cancer death (skin cancer is the most common, followed by prostate cancer for men and breast cancer for women).
The American Cancer Society estimates the U.S. will see about 230,000 new lung cancer cases this year and about 125,000 lung cancer deaths. Overall, about 5% of people will develop lung cancer; the risk is higher among smokers.
Often accompanying lung cancer is a debilitating muscle-wasting syndrome known as cachexia, which kills as many as 30% of the cancer patients it afflicts. People with cachexia will lose weight even if they eat, and not just fat but muscle mass as well.
"By loading our LNPs with follistatin mRNA, we developed a therapy that simultaneously targets lung cancer and cancer cachexia, all without adverse effects," Taratula said. "More preclinical work is necessary, but we're very encouraged by what we've seen so far and hope that testing in humans is down the road."
The College of Pharmacy's Vladislav Grigoriev, Tetiana Korzun, Ammar Salem, Kongbrailatpam Shitaljit Sharma, Prem Singh, Chrissa Kioussi and Olena Taratula also contributed to the research, as did Daniel Marks of Endevica Bio, a company that develops peptide therapies.
Supporting the study were the National Cancer Institute, the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Research Foundation of Korea.
