The goal of the Colorado Lung Cancer SPORE program is to conduct translational research studies that will lead to a reduction in the lung cancer mortality rates through improved early detection, prevention, and treatment. This goal is accomplished through four novel projects, a developmental research program, and a career development program all of which are supported by four interacting shared core resources. The future impact of the program will be to hasten translation of scientific discoveries from their development to approved human use of products and services benefiting patients. The projects proposed for this next cycle are Targeting FGFR Signaling in Lung Cancer (Proj. 1);Improving the Outcome of EGFR TKI Therapy Using Rational Combinations (Proj. 2);Prostacyclin and Peroxisome Proliferator-Activated Receptor-y in Lung Cancer (Proj. 3);and Predictors of Pulmonary Nodule Malignancy (Proj. 4). The proposed shared core resources are a Tissue Bank and Biomarkers Core (A);Clinical Trials Core (B);Biostatitistics/Bioinformatics/lnformatics Core (C);and Administrative Core (D). Each Core will facilitate the translation of the research conducted by the Projects. Our SPORE studies have already had a strong impact by contributing to a transformation in the way high risk subjects and lung cancer patients are approached and treated. We are proud of our role in: 1) the development and approval of EGFR TKI therapy coupled with predictive mariners for patient selection;2) the approval of crizotinib and the use of the FISH break-apart probe as a predictive biomarker;3) the use of etinostat (HDAC inhibitor) for improving outcome of EGFR TKI therapy;4) the huge potential of low dose spiral CT screening to reduce lung cancer mortality, especially if barriers can be overcome;5) changing the landscape of chemoprevention trials allowing rapid completion of moderately sized trials and the potential for a major national randomized phase III trial. We believe that our SPORE studies and collaboration have played a key role in the transformation of lung cancer diagnosis and therapy and that our proposed studies will be equally effective in bringing new products and approaches to lung cancer patients. We believe that we can continue our success in the next grant cycle with translation of discovery to early SPORE trials and handoff of more advanced discoveries to industry and cooperative groups.

Public Health Relevance

Our SPORE program is designed to provide advances in early detection, prevention, biomarkers, and therapy of lung cancer to improve the overall 5-year survival rates (currently only 16%). We will use a multi-disciplinary approach combining clinical and basic scientists to develop novel therapies, new chemoprevention strategies, improve outcomes from existing therapies, and explore more effective early detection strategies.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
2P50CA058187-19A1
Application #
8664635
Study Section
Special Emphasis Panel (ZCA1-RPRB-7 (J1))
Program Officer
Ujhazy, Peter
Project Start
1997-05-20
Project End
2019-04-30
Budget Start
2014-09-17
Budget End
2015-08-31
Support Year
19
Fiscal Year
2014
Total Cost
$2,162,000
Indirect Cost
$751,781
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Helfrich, Barbara A; Gao, Dexiang; Bunn Jr, Paul A (2018) Eribulin inhibits the growth of small cell lung cancer cell lines alone and with radiotherapy. Lung Cancer 118:148-154
Kleczko, Emily K; Heasley, Lynn E (2018) Mechanisms of rapid cancer cell reprogramming initiated by targeted receptor tyrosine kinase inhibitors and inherent therapeutic vulnerabilities. Mol Cancer 17:60
McCoach, Caroline E; Le, Anh T; Gowan, Katherine et al. (2018) Resistance Mechanisms to Targeted Therapies in ROS1+ and ALK+ Non-small Cell Lung Cancer. Clin Cancer Res 24:3334-3347
Drilon, Alexander; Laetsch, Theodore W; Kummar, Shivaani et al. (2018) Efficacy of Larotrectinib in TRK Fusion-Positive Cancers in Adults and Children. N Engl J Med 378:731-739
Pilling, Amanda B; Kim, Jihye; Estrada-Bernal, Adriana et al. (2018) ALK is a critical regulator of the MYC-signaling axis in ALK positive lung cancer. Oncotarget 9:8823-8835
Kwak, Jeff W; Laskowski, Jennifer; Li, Howard Y et al. (2018) Complement Activation via a C3a Receptor Pathway Alters CD4+ T Lymphocytes and Mediates Lung Cancer Progression. Cancer Res 78:143-156
Sakamoto, Mandy R; Honce, Justin M; Lindquist, Deborah L et al. (2018) Lorlatinib Salvages CNS Relapse in an ALK-Positive Non-Small-Cell Lung Cancer Patient Previously Treated With Crizotinib and High-Dose Brigatinib. Clin Lung Cancer :
McCoach, Caroline E; Blakely, Collin M; Banks, Kimberly C et al. (2018) Clinical Utility of Cell-Free DNA for the Detection of ALK Fusions and Genomic Mechanisms of ALK Inhibitor Resistance in Non-Small Cell Lung Cancer. Clin Cancer Res 24:2758-2770
Geraci, Mark W (2018) TARGETING THE PROSTACYCLIN/PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA AXIS IN LUNG CANCER CHEMOPREVENTION. Trans Am Clin Climatol Assoc 129:48-55
Robichaux, Jacqulyne P; Elamin, Yasir Y; Tan, Zhi et al. (2018) Mechanisms and clinical activity of an EGFR and HER2 exon 20-selective kinase inhibitor in non-small cell lung cancer. Nat Med 24:638-646

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