? Lung cancer is one of the most common cancers in the US and is the number one cause of cancer death for both men and women in the Western world. The high mortality among patients with lung cancer is mainly due to the absence of an effective screening strategy and the lack of effective therapy for many patients. Lung adenocarcinoma can be challenging to diagnose at an early curable stage when surgery is warranted and represents the best treatment available. Unfortunately, even these patients who undergo seemingly curative surgery have a 30-40% mortality and usually die from recurrent cancer. A diagnostic test capable of earlier detection and accurate diagnosis of lung cancer will contribute to the development of screening strategies. Similarly, a lung cancer prognostic test that can identify those patients not likely to respond to surgery will dramatically impact clinical treatment, and by extension survival. One objective of this laboratory is to address insufficiencies in lung cancer screening strategies. To this end, we have created novel ratio-based diagnostic and prognostic tests for lung cancer that has been highly accurate in multiple studies to this point. Since these tests are especially suited to clinical use, they can therefore be rapidly and easily incorporated into proposed lung cancer screening strategies by analyzing fine needle aspiration (FNA) biopsies obtained in response to an abnormal spiral computerized tomography (CT) chest scan in patients with suspected lung cancer. The explicit goal of this proposal is to further confirm the accuracy and reproducibility of gene ratio-based detection, diagnosis, and prognosis in lung cancer in a larger number of samples to justify a multi-center clinical trial.
The specific aims of this proposal are: ? Specific Aim 1. To determine whether gene ratios can be used to accurately detect and diagnose lung cancer in a retrospective cohort of frozen normal lung and tumor discarded surgical specimens. ? Specific Aim 2. To determine if gene ratios can be used to detect and diagnose lung cancer in tissues obtained from FNA. ? Specific Aim 3. To determine whether gene ratios can be used to accurately predict clinical outcome (i.e. survival) in patients with stage I lung adenocarcinoma who underwent surgery with curative intent. ? Specific Aim 4. To develop software for the expression ratio test and to design a form summarizing the results of the diagnostic test kit to clinicians and health care personnel. ? ?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA105249-02
Application #
6803524
Study Section
Special Emphasis Panel (ZCA1-SRRB-Q (O1))
Program Officer
Krueger, Karl E
Project Start
2003-09-30
Project End
2006-08-31
Budget Start
2004-09-15
Budget End
2006-08-31
Support Year
2
Fiscal Year
2004
Total Cost
$86,500
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Gordon, G J; Mani, M; Mukhopadhyay, L et al. (2007) Expression patterns of inhibitor of apoptosis proteins in malignant pleural mesothelioma. J Pathol 211:447-54
Gordon, Gavin J; Deters, Levi A; Nitz, Matthew D et al. (2006) Differential diagnosis of solitary lung nodules with gene expression ratios. J Thorac Cardiovasc Surg 132:621-7
Gordon, Gavin J; Rockwell, Graham N; Jensen, Roderick V et al. (2005) Identification of novel candidate oncogenes and tumor suppressors in malignant pleural mesothelioma using large-scale transcriptional profiling. Am J Pathol 166:1827-40
Gordon, Gavin J; Rockwell, Graham N; Godfrey, Paul A et al. (2005) Validation of genomics-based prognostic tests in malignant pleural mesothelioma. Clin Cancer Res 11:4406-14