The studies were conducted by the University of Texas MD Anderson Cancer Center and the University of Texas Southwestern Medical Center.
Two tumor-suppressing genes given intravenously reduced cancer separately but had their most powerful effect when administered together, cutting the number of tumors per mouse by 75% and the weight of tumors by 80%.
“In cancer treatment we have combination chemotherapy, and we also combine different modes of therapy – surgery, radiation and chemotherapy. Now you’ve got the possibility of combined targeted gene therapy,” said Jack Roth, professor and chair of the MD Anderson Department of Thoracic and Cardiovascular Surgery.
The genes wrapped in the nanoparticles were p53, a well-known tumor suppressor that works by causing defective cells to commit suicide and is often shut down or defective in cancer cells, and FUS1, a tumor-suppressor discovered by the research group that is deficient in most human lung cancers.
The researchers reported that FUS1 works with p53 to force the lung cancer cells to kill themselves, a process known as apoptosis. The cancer cell lines treated with the gene combination had 2 to 3 times more cells killed by apoptosis than either gene nanoparticle had individually.
“We certainly hope this approach will be more effective but we also think it’s likely to be much less toxic, with fewer side effects, than other types of combined cancer therapy,” said Jack Roth.
The research team expects to advance combination therapies to clinical trials in the coming years, either of genes or of genes with other biologic or chemotherapy agents.