Cancer Research Lab

Co-expression of the novel tumor suppressor gene FUS1 and the well-established p53 is associated with enhanced suppression of human non-small cell lung cancer (NSCLC) in mice, investigators report in the January 15th issue of Cancer Research.

The enhanced anti-oncogene expression was accomplished by nanoparticle-mediated gene transfer. Senior researcher Dr. Lin Ji told Reuters Health, “The synergistic antitumor effects observed by systemic delivery of nanoparticles combining two novel tumor suppressor genes in pre-clinical lung cancer animal models would offer a more effective molecular therapeutic strategy for lung cancer and other human cancers.”

Dr. Ji of The University of Texas M.D. Anderson Cancer Center, Houston, and colleagues note that loss of expression and other FUS1 protein problems have been found in a majority of human lung cancers. Restoration of wild-type FUSI, they add, in deficient human lung cancer cells has led to potent tumor suppression.

The team found that co-expression of FUSI and p53 by cholesterol nanoparticle-mediated gene transfer, significantly and synergistically inhibited NSCLC cell growth and induced apoptosis in vitro.

In a human lung cancer orthotopic mouse model, systemic treatment with a combination of FUSI and p53 nanoparticles synergistically suppressed the development and growth of tumors.

The synergistic effect, say the investigators, appears to be due to the fact that FUS1 suppresses a gene expressing a protein known to rapidly degrade p53.

These results, the researchers conclude, “provide new insights into the molecular mechanism of FUSI-mediated tumor suppression activity and imply that a molecular therapy combining two or more functionally synergistic tumor suppressors may constitute a novel and effective strategy for cancer treatment.”

Furthermore, Dr. Ji added, “a phase I clinical trial using the same FUS1-nanoparticles mentioned in this article has been approved by FDA and is (under way) in later stage lung cancer patients at M.D. Anderson Cancer Center.”