Cleveland Clinic Foundation
Mapping and Exploiting the Subclonal Architecture of Lung Adenocarcinoma
While recent large-scale sequencing studies of cancers have revealed their overall mutational landscapes, they have largely disregarded the individual genetic diversity that has been identified in most solid tumors, which has critical consequences for tailoring personalized cancer patient care. The distinct subclones that constitute this intra-tumoral diversity are dynamic in response to inherent genetic drift or selection related to anti-cancer treatments. Thus, the sampling of a tumor for genomic analyses in a fixed time and space offers only a restricted view of its genetic composition. For this reason, we have developed mathematical and experimental models to study the stratification of tumor subclones in topographic space and time. Upon completion, our work will provide a greater understanding of subclonal tumor dynamics and advance new strategies that seeks to exploit our understanding of clonal architecture to improve the care of patients with lung cancer.
Update: I am focused on studying recently discovered genomic alterations in order to better understand and therapeutically target cancers. This year, we studied the role of mutations in the BRAF gene and the mitogen-activated protein kinase (MEKI) in lung cancer. We showed that certain BRAF variants are more likely to survive radiation therapy. We also demonstrated that the efficacy of concurrent treatments using targeted therapies and radiation can vary based on the type of BRAF variant. Our results indicate that treatments that antagonize MEK1 can be potent therapeutic sensitizers in cells containing certain mutations in BRAF. This finding may lead to an effective treatment strategy in these tumors.