The AACR Dharma Master Jiantai Innovative Grant for Lung Cancer Research provides additional funding to an investigator for an existing project that develops and studies new ideas and approaches that have direct application and relevance to lung cancer. Following the Grant-in-Aid of Research model, this support supplements existing funding for an investigator conducting a basic or translational research project that will contribute to the acceleration of progress against lung cancer, for the ultimate goal of improving patient care.
Julie M. Wells, Ph.D.
Research Scientist, The Jackson Laboratory, Bar Harbor, ME
Detecting Changes in Circulating MicroRNAs During Lung Cancer Progression
"Greater than 90 percent of cancer mortality is attributable to metastasis yet the biological mechanisms controlling metastasis are incompletely understood. MicroRNAs (miRNAs) are important regulators of gene expression during diverse biological processes and compelling experimental data suggests a role for miRNAs during lung cancer progression. In an effort to better characterize the role of individual miRNAs in cancer progression, we are developing an assay to identify the changes in microRNA expression and target affinities that define the transition from early-stage to late-stage pulmonary adenocarcinomas in genetically engineered mice. Toward this goal, we are utilizing two different strains of mice: the first strain carries a single mutation in the cellular oncogene Kras while the second strain carries both the Kras mutation and a second mutation in the tumor suppressor gene p53. Both strains of mice develop very high frequencies of lung tumors that resemble human pulmonary adenocarcinomas, but only tumors within the double mutant mice display features of late-stage disease including metastasis. The objective of this proposal is to determine if circulating miRNAs from these two strains of mice provide reliable biomarkers of lung cancer progression. For these studies, we will sample serum and measure miRNA expression at multiple times during a defined, reproducible lung tumor progression timeline and compare changes in serum miRNA expression to changes in tumor miRNA expression. Results from this study will be applicable to using serum miRNAs as a predictor of tumor initiation and progression, to monitor responses to chemotherapeutic treatments in animal models and potentially for screening at risk human populations for the presence of lung cancer."
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Katrina A. Steiling, M.D., M.Sc.
Assistant Professor of Medicine, Boston University Medical Campus, Boston, MA
Airway Genomics for the Early Detection of Lung Cancer
"Nearly 100 million current and former smokers are at increased risk for lung cancer, and 10-20 percent will ultimately develop this disease. While clinical risk factors can identify current and former smokers at highest risk for lung cancer, we lack sensitive and specific tests for diagnosing lung cancer at early stages where treatment is most successful. We have previously shown that the cells that line the airway are altered by smoking and that specific responses, as measured by the pattern of gene expression in these cells, are associated with and potentially precede the development of lung cancer. Cancer-specific differences in airway epithelial cells that can be readily collected as part of routine clinical care might, therefore, be able to serve as a sentinel for detecting tumors deeper in the lungs that might otherwise be invisible. To achieve this goal, it is important to have a more complete catalog of all the cancer-specific differences in these cells that could be the basis of diagnostic tests for lung cancer. The objective of this proposal, therefore, is to use new sequencing technology that is able to create a detailed profile of exactly what parts of the genome are being actively transcribed and how these transcripts are processed to perform a thorough search for cancer-associated differences in the transcriptome of airway epithelium."
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