Small Cell Lung Cancer (SCLC) is a very aggressive form of lung cancer with few treatment options. This is due, in part, to an incomplete understanding of the ways by which this cancer develops. Recent genomic analyses have identified genes that are mutated and nonfunctional in SCLC indicating that they may play an important role. Interestingly, several of those genes encode for proteins that make up a large protein complex. The normal function of this complex is to manage how DNA is organized and packed inside the nucleus of a cell. We don’t know whether and how the inactivation of this complex promotes the development of SCLC. To address this question, we have developed new biological models in which the complex can either be inactivated or reactivated. Interestingly, we have found that blocking its normal function accelerates the development of SCLC. With the support of the V Foundation, we will assess how inactivation of the complex affects DNA organization and the expression of genes. We will also use the information we learn to find new strategies to eradicate these tumors. The proposed research will lead to a better understanding of the ways by which SCLC forms and may identify more effective treatments for patients diagnosed with SCLC.
Arnaud Augert, Ph.D.
Location: Yale Cancer Center - Connecticut
Proposal: Dissecting the transcriptional and epigenetic mechanisms underlying small cell lung cancer initiation and progression