Abstract IA03: Genomic and epigenomic targets in small cell lung cancer.

Recent comprehensive analyses of the genome, transcriptome, and proteome of small cell lung cancer (SCLC) have provided new insights into the biology of this particularly aggressive cancer type. As has been known for several years, most SCLC demonstrate concomitant loss or inactivation of two key tumor suppressors, p53 and RB; conditional loss of these genes in a mouse model results in lung cancer with many of the properties of human SCLC. Amplification and aberrant expression of MYC family members, including L-MYC and N-MYC, are strongly implicated in SCLC. Other important oncogenes amplified in subsets of SCLC include SOX2, a key developmental transcription factor, and the receptor tyrosine kinase FGFR1. Several key epigenetic control genes are mutated or disregulated in SCLC, including EZH2. Recent analyses of the SCLC methylome suggest that these cancers may be categorized into subsets based on global gene expression and methylation patterns. Taken together with recent proteomic studies highlighting additional potential targets including PARP1, these recent observations are providing a new landscape of investigational therapeutic opportunities for SCLC.

Citation Format: Charles M. Rudin. Genomic and epigenomic targets in small cell lung cancer. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr IA03.