The Johns Hopkins Lung Cancer SPORE is in its fourteenth year and continues to have as its goals, the performance of highly translational research to provide new means for the prevention of, risk assessment for, early detection of, gauging prognosis of, and therapy for, lung cancers of all types. Our work encompasses collaboration with other Lung Cancer SPORE'S, extensive leveraging of foundation, institutional, and commercial partnering support, and interaction with other NCI initiatives. We use flexibility of the SPORE funding mechanism to extend projects that continually evolve higher and higher translational potential and curtail those that do not. We emphasize incorporation of new concepts and directions to facilitate development of areas that are headed for ultimate translational verification and even movement to common clinical practice. Two projects, Projects 1 and 2, the latter a collaborative venture with the Colorado SPORE, stress biomarker research at the highest translational level. Both involve highest translational level validation of gene DNA hypermethylation markers with high promise for: a) in assays of tumor and lymph node DNA, restaging stage 1 to stage 3 lung cancer and predicting patients with highest risk for rapid disease recurrence;and b) in assays of sputum DNA, predicting individuals at highest risk for imminent development of lung cancer and /or facilitating early diagnosis of the disease. In both projects, implications of the markers for developing epigenetic approaches to adjuvant therapy and prevention will be directly explored. This work also links participation of the Hopkins SPORE with the consortium lloprost chemoprevention trials (Lung Cancer Biomarker Chemoprevention Consortium-LCBCC) involving other Lung Cancer SPORES and, especially, the Colorado SPORE. In terms of developing novel lung cancer therapies, Project 4 is at a very high translational level with correlative science to be conducted in the setting of first in human clinical trials for the inhibition of the enzyme, fatty acid synthase. Project 3, will explore the correlation, in non-small cell lung cancer, of newly found frequent mutations in the NRF2 stress response pathway, that renders this protein constitutively active in the nucleus, with the presence of drug resistance to commonly employed treatment regimens and the possibilities for inhibiting this pathway to reverse chemoresistance.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA058184-15
Application #
7753899
Study Section
Special Emphasis Panel (ZCA1-GRB-I (O1))
Program Officer
Ujhazy, Peter
Project Start
1997-09-05
Project End
2013-11-30
Budget Start
2009-12-01
Budget End
2010-11-30
Support Year
15
Fiscal Year
2010
Total Cost
$1,710,038
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Hulbert, Alicia; Jusue-Torres, Ignacio; Stark, Alejandro et al. (2017) Early Detection of Lung Cancer Using DNA Promoter Hypermethylation in Plasma and Sputum. Clin Cancer Res 23:1998-2005
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Singh, Anju; Venkannagari, Sreedhar; Oh, Kyu H et al. (2016) Small Molecule Inhibitor of NRF2 Selectively Intervenes Therapeutic Resistance in KEAP1-Deficient NSCLC Tumors. ACS Chem Biol 11:3214-3225
Chiappinelli, Katherine B; Strissel, Pamela L; Desrichard, Alexis et al. (2015) Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses. Cell 162:974-86
Vendetti, Frank P; Topper, Michael; Huang, Peng et al. (2015) Evaluation of azacitidine and entinostat as sensitization agents to cytotoxic chemotherapy in preclinical models of non-small cell lung cancer. Oncotarget 6:56-70
Belinsky, Steven A (2015) Unmasking the lung cancer epigenome. Annu Rev Physiol 77:453-74
Sussan, Thomas E; Gajghate, Sachin; Thimmulappa, Rajesh K et al. (2015) Exposure to electronic cigarettes impairs pulmonary anti-bacterial and anti-viral defenses in a mouse model. PLoS One 10:e0116861
Kim, Jung-Hyun; Thimmulappa, Rajesh K; Kumar, Vineet et al. (2014) NRF2-mediated Notch pathway activation enhances hematopoietic reconstitution following myelosuppressive radiation. J Clin Invest 124:730-41
Ahuja, Nita; Easwaran, Hariharan; Baylin, Stephen B (2014) Harnessing the potential of epigenetic therapy to target solid tumors. J Clin Invest 124:56-63

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