Targeting Resistance in Colorectal Cancer with a Novel Lineage-Tracking Technology
Technical Report,01 Aug 2018,31 Jul 2019
The University of Texas at Austin Austin United States
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This proposal addresses the FY17 PRCRP Topic Area of Colorectal Cancer and the Military Relevance Focus Area Gaps in cancer prognosis, treatment andor survivorship that impact the health of military service members, veterans, and their beneficiaries. Treatment of colorectal cancer is complicated by the high degree of intratumoral heterogeneity. Recent studies have demonstrated the utility of DNA barcode libraries in monitoring heterogeneous cell populations. This is achieved by labeling each cell with a unique, heritable sequence lineage abundance is tracked over time by sequencing the barcode ensemble. Changes in clonal dynamics after perturbations, such as treatment with a pharmacological agent, reveal variation in lineage survival or growth rate.This approach enables the simultaneous observation of many lineage trajectories to reveal high-resolution details of cancer population dynamics. With this tool, the ability to concurrently track clonal fitness dynamics and generate lineage-specific genomic and transcriptomic data over longitudinal studies provides new insight into the response to therapeutics.
- Medicine and Medical Research