High-Throughput Functional Validation of Progression Drivers in Lung Adenocarcinoma
Final rept. 1 Sep 2012-31 Aug 2014
M D ANDERSON CANCER CENTER HOUSTON TX
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The primary objective of our Early Investigator Synergistic Idea Award is to establish a driver prioritization pipeline to functionally evaluate lung cancer genomics data to identify somatic driver aberrations, which beyond the handful of well-characterized genes like oncogenic KRAS, contribute to lung cancer progression. As outlined in our FinalReport, we have successfully constructed the necessary gene libraries for the screens outlined in the proposal Aim 1, optimized and conducted the proposed in vitro and in vivo screens Aim 2. We have already identified several robust drivers of cell invasion and in vivo metastasis. After prioritizing our list of hits by filtering through clinical datasets, we have the necessary tools in place for further mechanistic studies of lead candidate genes Aim 3, including our development of a novel isogenic human bronchial epithelial cell system that permits regulatible expression of the KRAS oncogene. We have made several technical improvements to the overall work flow of our functionalization pipeline and view this as a successful project that will facilitate further screening of emerging lung cancer genomics datasets extending well past the life of this particular grant.
- Medicine and Medical Research