Hui-Zi Chen, MD, PhD

Small cell lung cancer (SCLC) is a type of lung cancer that is exceedingly difficult to treat. The five-year overall survival of patients diagnosed with this cancer is estimated to be approximately 7%. For almost 40 years, there were no new therapies approved for SCLC, for either newly diagnosed patients or those who have relapsed. More research is needed to understand why SCLC is so biologically aggressive in order to develop new treatments. This proposal will focus on a subset of SCLC patients whose tumors have mutations in a gene called KMT2D, which has important functions in controlling the 'epigenome' of cells. Epigenome is a collection of reversible chemical modifications to DNA or histone proteins that can turn genes on or off. Our research will identify which gene pathways are impacted by KMT2D mutations in SCLC and whether they may be targeted by existing therapies or spur the development of new drugs.

Update: My lab is studying KMT2D, a protein that may play an important role in suppressing small cell lung cancer (SCLC) development. In the first year of the project, we analyzed the mutational status of this KMT2D in approximately 1,700 real-world SCLC patients, gathering patient data being treated in routine medical settings rather than relying on clinical trial data. We identified loss-of-function mutations in KMT2D in approximately 13% of these patients. This relatively high mutation rate suggests that SCLC patients with KMT2D mutations in their tumor may be treated with specific therapies. In the second year of the project, we are now on track to determine what effects on tumor initiation and/or growth are caused by the loss of KMT2D function in SCLC cell lines, in part through analyzing how KMT2D affects the three-dimensional organization of DNA inside the nuclei of SCLC cancer cells.