Lung and Thoracic Cancer Research at the University of Colorado Cancer Center

Featured Researcher

Fred Hirsch, MD, PhD, is professor of Medicine and Pathology at the University of Colorado Denver. He is an international expert on early detection and treatment of lung cancer. His current work focuses on the role of  epithelial growth factor (EGFR) inhibitors in lung cancer, and how to select patients based on molecular markers. He is also focused on developing biomarkers for early detection of lung cancer.

Dr. Hirsch is co-Principal Investigator on the UCCC Lung SPORE and co-director of the SPORE's tissue bank. He is a member of the International Association for the Study of Lung Cancer (IASLC) board of directors, and has been a member of the World Health Organization Expert Panel for Classification of Lung Tumors for many years. He is also is the co-chair of the Lung Cancer Translational Science Committee for the Southwest Oncology Group.

In 2007, Dr. Hirsch received the IASLC Mary Matthews Distinguished Award for Translational Research in Lung Cancer.

The University of Colorado Cancer Center's Thoracic Oncology (Lung Cancer) Research programs are world renowned. Some of the world's most respected basic, clinical and translational researchers work here. Our outstanding team of clinical and laboratory researchers work together to improve the outlook for all patients affected by lung cancer and a range of other thoracic/chest cancers, by leading research into cancer prevention, early detection and treatment. Our researchers include:

• specialized molecular biologists
• cytogeneticists
• pathologists
• pulmonologists
• radiologists
• thoracic surgeons
• radiation oncologists
• medical oncologists

Recent Successes

The UCCC Thoracic Oncology Program comprises both laboratory and clinical researchers who have driven, and continue to drive, many of the latest breakthroughs in the understanding and treatment of lung/thoracic cancers. Research is funded through a combination of government and other academic grants, industrial collaborations, and individual gifts and donations. Recent successes include:

• Multiple successes in defining molecular signatures that predict response or resistance to therapy in lung cancer patients treated with EGFR inhibitors.
• The discovery and defining of numerous biomarkers of lung cancer risk in bronchial epithelium.
• Completion of a large randomized multi-center chemoprevention study of Iloprost in individuals at high risk of developing lung cancer — a drug chosen based on UCCC’s increased understanding of the lung cancer development process.
• Increasing lung cancer patients’ access to promising new drugs through direct links with the UCCC Developmental Therapeutics Program.
• Tripling the number of UCCC lung cancer patients put on therapeutic clinical trials between 2005 and 2007.

Recent Publications

Exploration of molecular signatures for the development of lung cancer induced by cigarette smoke

• Stearman RS, Dwyer-Nield L, Grady MC, Malkinson AM, Geraci MW. A unique macrophage gene expression signature defines a field effect in the lung tumor microenvironment. Cancer Research 2007
• Miller YE, Blatchford P, Hyun DS, Keith RL, Kennedy TC, Wolf H, Byers T, Bunn PA Jr, Lewis MT, Franklin WA, Hirsch FR, Kittelson J. Bronchial epithelial Ki-67 index is related to histology, smoking and gender, but not lung cancer or chronic obstructive pulmonary disease. Cancer Epidemiol Biomarkers Prev. 2007 Nov;16(11):2425-31
• Varella-Garcia M, Chen L, Powell RL, Hirsch FR, Kennedy TC, Keith R, Miller YE, Mitchell JD, Franklin WA. Spectral karyotyping detects chromosome damage in bronchial cells of smokers and patients with cancer. Am J Respir Crit Care Med. 2007 Sep1;176(5):505-12

Early detection of lung cancer at bronchoscopy through defining high-risk cellular patterns

• Jonsson S, Varella-Garcia M, Miller YE, Wolf HJ, Byers T, Braudick S, Kiatsimkul P, Lewis M, Kennedy TC, Keith RL, Bjornsson J, McWilliams A, Lam S, Hirsch FR, Franklin WA. Chromosomal aneusomy in bronchial high grade lesions is associated with invasive lung cancer. American Journal of Respiratory and Critical Care Medicine 2007, (In press)

Identification of molecular signatures that predict for lung cancer responses to specific drug treatment (EGFR inhibition) in the laboratory, and validation of these signatures in patients within the clinical trial setting

• Helfrich BA, Raben D, Varella-Garcia M, Gustafson D, Chan DC, Bemis L, Coldren C, Baron A, Zeng C, Franklin W, Hirsch FR, Gazdar A, Minna J, Bunn PA. Antitumor activity of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib in non-small cell lung cancer cell lines correlates with gene copy number and EGFR mutations but not EGFR protein levels. Clinical Cancer Research 2006; 12(3): 7117-7125
• Hirsch FR, Varella-Garcia M, Bunn PA, Franklin WA, Dziadziuszko R, Thatcher N, Chang A, Parikh P, Pereira JR, Ciuleanu T, von Pawel J, Watkins C, Flanner A, Ellison G, Donald E, Knight L, Parums D, Botwood N, Holloway B. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small cell lung cancer. Journal of Clinical Oncology 2006; 24(31):5034-5042
• Taguchi F, Solomon B, Gregore V, Roder H, Gray R, Kasahara K, Nishio M, Brahmer J, Spreafico A, Ludovini V, Massion PP, Dziadziuszko R, Schiller J, Grigorieva J, Tsypin M, Hunsucher SW, Caprioli R, Duncan MW, Hirsch FR, Bunn PA Jr, Carbone DP. Mass spectometry to classify non-small-cell lung cancer patients for clinical outcomes after treatment with epidermal growth factor receptor tyrosine kinase inhibitors: a multicohor cross-institutional study. J Natl Cancer Inst. 2007 Jun 6;99(11):838-46
• Hirsch FR, Varella-Garcia M, Cappuzzo F, McCoy J, Bemis L, Xavier AC, Dziadziuszko R, Gumerlock P, Chansky K, West H, Gazdar AF, Crino L, Gandara DR, Franklin WA, Bunn PA Jr. Combination of EGFR gene copy number and protein expression predicts outcome for advanced non-small-cell lung cancer patients treated with gefitinib. Ann Oncol. 2007 Apr;18(4):752-60. Epub 2007 Feb 22
• Coldren CD, Helfrich BA, Witta SE, Sugita M, Lapadat R, Zeng C, Baron A, Franklin WA, Hirsch FR, Geraci MW, Bunn PA Jr. Baseline gene expression predicts sensitivity to gefitinib in non-small-cell lung cancer cell lines. Mol Cancer Res. 2006 Aug;4(8):521-8
• Hirsch FR, Varella-Garcia M, McCoy J, West H, Xavier AC, Gumerloc P, Bunn PA Jr, Franklin WA, Crowley J, Gandara DR, Southwest Oncology Group. Increased epidermal growth factor receptor gene copy number detected by fluoresence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J Clin Oncolo. 2005 Oct 1; 23(28):6838-45. Epub 2005 Jul 5.
• Capuzzo F, Hirsch FR, Rossi E, Barolini S, Ceresoli GL, Bemis L, Haney J, Witta S, Danenberg K, Domenichini I, Ludovini V, Magrini E, Gregorc V, Dolioni C, Sindoinii A, Tonato M, Franklin WA, Crino L, Bunn PA Jr, Varella-Garcia M. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005 May 4;97(9): 643-55

Discovery of molecules controlling key signalling pathways within lung cancer cells that may become future drug targets

• Potiron VA, Sharma G, Nasarre P, Clarhaut JA, Augustin HG, Gemmill RM, Roche J, Drabkin HA. Smeaphorin SEMA3F affects multiple signalling pathways in lung cancer cells. Cancer Research 2007, 67(18):8708-8716