Researchers have discovered that the gene EP300 can both inhibit and promote small-cell lung cancer (SCLC). By manipulating the gene, the researchers were able to stop the spread of cancer in mouse models. The scientists hope that this new approach might lead to better treatments for a range of cancers. The research, which appears in the journal Science Advances, lays the groundwork for developing future cancer treatments for humans.
Living with lung cancer? Here are the facts you need Get evidence-based information and expert recommendations delivered to your inbox with our 3-day limited series. An estimated 13% of diagnosed lung cancer is SCLC. According to the National Organization for Rare Diseases, SCLC is an aggressive type of cancer “characterized by rapid, uncontrolled growth of certain cells in the lungs.”
If SCLC is caught early and before it has spread, treatments can control the disease in up to 25% of cases. The authors of the recent study wanted to understand the role of EP300 gene mutations in SCLC. Medical News Today spoke with the corresponding authors of the study: Dr. Kwon-Sik Park — associate professor of microbiology, immunology, and cancer biology at the University of Virginia School of Medicine in Charlottesville.
Dr. John Bushweller — professor of molecular physiology and biological physics at the University of Virginia. “The current prognosis for SCLC patients is particularly poor with only 7% of patients surviving beyond 5 years. This reflects a lack of well-validated targets for therapy and a concomitant lack of targeted agents to treat the disease,” they explained.
“It is critical to garner further insights as to the drivers of the disease as well as develop drugs targeting those drivers. However, relevant pre-clinical models of SCLC carrying recurrent driver mutations were scarce, precluding the study to assess the physiological role of the mutations and the therapeutic impact of restoring their normal functions. So we built pre-clinical models using genetically engineered mice and cells.” By studying genetically engineered mouse models, the researchers found that EP300 — the protein that the EP300 gene codes for — can either promote or inhibit SCLC.
Specifically, they found that part of the EP300 protein — known as the KIX domain — was essential for the development of SCLC. “EP300 is a multi-functional protein and loss of its histone acetyltransferase domain function — as predicted based on the mutations observed in SCLC patient tumors — drives the cancer. This idea was validated by the findings from the pre-clinical models,” they explained.
“Unexpectedly, however, the models also showed that the KIX domain of the mutant EP300, which remains intact, drives the disease.
