2015 Lung Cancer Research Foundation Annual Grant Program
Carla Kim, PhD
Boston Children's Hospital
Research Project:
Precision medicine opportunities for BRG1 deficient lung cancers
Summary:
Sequencing of lung cancer genomes has revealed common alterations in the SMARCA4/BRG1 gene, which encodes the BRG1 component of the SWI/SNF chromatin-remodeling complex. Given that up to 40% of lung adenocarcinomas have mutations in this gene, a precision medicine option for this genotype of lung cancer would benefit a large number of patients. Recently, Dr. Kim and her team identified a rationale for combining the common chemotherapy etoposide with an inhibitor of the epigenetic enzyme EZH2 for more effective outcomes in BRG1 mutant lung cancers. To learn the mechanisms for this drug synergy, the Kim laboratory is now using novel genome engineering approaches based on the CRISPR-Cas9 system to generate precise models of human origin to study the effects ofBRG1 mutation in tumorigenesis and therapeutic response. These systems will be used to study the effects of this specific drug combination, as well as to identify additional precision medicine opportunities for these cancers.
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