The researchers, led by UVA's Kwon-Sik Park, Ph.D., and John H. Bushweller, Ph.D., were seeking to understand the role of a mutation in the EP300 gene in the formation of small-cell lung cancer tumors. Their experiments revealed that the gene makes a protein with surprising properties that can both foster or prevent the development of small-cell lung cancer. By preventing the gene from acting as a tumor-promoter, the researchers were able to stop the cancer from forming and spreading. This held true in both cell samples and lab mice.
The protein's essential role in tumor formation makes it an enticing target for researchers seeking to development new treatments for small-cell lung cancer (SCLC), an exceptionally dangerous form of cancer. Overall five-year survival for patients diagnosed with SCLC is only about 7%.
"The most remarkable aspect of our findings is that we explained the unique vulnerability of EP300 at the molecular level, down to a single amino acid," said Park, of the University of Virginia School of Medicine's Department of Microbiology, Immunology and Cancer Biology. "Given the frequent EP300 mutations found in a wide range of cancer types, I hope that the concept of targeting the EP300 KIX domain will have a more general applicability for cancer therapy." ...