Tracing Tumor Progression in KRAS-driven Cancers

Although it has become increasing clear that cancers display significant cellular heterogeneity, the spatial growth dynamics of genetically distinct clones within developing solid tumors remain poorly understood. Leveraging the mosaic analysis with double markers (MADM) system, we have traced subclonal populations retaining or lacking p53 within oncogenic KRAS-initiated lung and pancreatic tumors. In both tumor types, p53 loss is permissive but not sufficient for progression to advanced adenocarcinoma. By applying single cell molecular analyses of cells isolated from these models, we hope to uncover novel mediators of tumor progression, which may represent targets for cancer interception.