Our overarching goal is to develop biomarkers that are useful in informing clinical management of CT detected lung nodules of indeterminate etiology. Biomarkers assayed in non-invasively obtained biospecimens need to be developed to enhance the performance of currently evolving lung cancer risk models which are based solely on demographics, clinical and imaging characteristics. We hypothesize: 1. Biomarkers measurable in non-invasively obtained specimens can discriminate between benign and malignant lung nodules detected by CT. 2. These biomarkers can be incorporated into a prediction model to aid clinical decision making and potentially improve outcomes by shortening time to diagnosis of lung cancer, decreasing biopsy and/or surgery for benign disease, reducing patient anxiety and decreasing costs. In the current SPORE grant period, we have developed several promising biomarkers and carried out initial validation steps. We now are in the position to assess these prospectively and simultaneously in a population in which they would have immediate clinical applicability, through the following Specific Aims: 1. Develop and test novel measurement tools for the following biomarkers in non-invasively obtained specimens, including: a) Epithelial chromosomal imbalances;b) Circulating protein levels;c) Exhaled breath volatile organic compounds;d) miRNA expression patterns. 2. Compare the performance of the individual biomarkers singly and in combinations in discriminating benign from malignant nodules in a cohort of subjects with indeterminate lung nodules referred to specialty clinics for evaluation. 3. Develop a model based on biomarker outcomes, smoking history, clinical and imaging features for the prediction of malignancy in CT detected lung nodules. We envision that at the end of this project, the above predictive model can be subjected to further prospective validation in independent cohorts of patients with indeterminate CT detected lung nodules, in which changes in specific outcomes (time to diagnosis, invasive procedures for benign disease, costs) can be simulated.
Low dose CT screening for lung cancer has now been demonstrated to result in a reduction in both overall and lung cancer specific mortality, but with a high false positive rate which leads to patient anxiety, unnecessary invasive procedures, delays in diagnosis and costs. Biomarkers have the potential to improve the clinical management of CT detected lung nodules. This project will evaluate 4 promising biomarkers prospectively and simultaneously in the setting of indeterminate lung nodules;we will incorporate results into a predictive model to aid in clinical management.
|Symonds, Jennifer M; Ohm, Angela M; Tan, Aik-Choon et al. (2016) PKCÎ´ regulates integrin Î±VÎ²3 expression and transformed growth of K-ras dependent lung cancer cells. Oncotarget 7:17905-19|
|Dziadziuszko, Rafal; Le, Anh T; Wrona, Anna et al. (2016) An Activating KIT Mutation Induces Crizotinib Resistance in ROS1-Positive Lung Cancer. J Thorac Oncol 11:1273-81|
|Saichaemchan, S; Ariyawutyakorn, W; Varella-Garcia, M (2016) Fibroblast Growth Factor Receptors: From the Oncogenic Pathway to Targeted Therapy. Curr Mol Med 16:40-62|
|Scarborough, Hannah A; Helfrich, Barbara A; Casas-Selves, Matias et al. (2016) AZ1366: An inhibitor of tankyrase and the canonical Wnt pathway that limits the persistence of non-small cell lung cancer cells following EGFR inhibition. Clin Cancer Res :|
|Poczobutt, Joanna M; Nguyen, Teresa T; Hanson, Dwight et al. (2016) Deletion of 5-Lipoxygenase in the Tumor Microenvironment Promotes Lung Cancer Progression and Metastasis through Regulating T Cell Recruitment. J Immunol 196:891-901|
|Li, Bob T; Ross, Dara S; Aisner, Dara L et al. (2016) HER2 Amplification and HER2 Mutation Are Distinct Molecular Targets in Lung Cancers. J Thorac Oncol 11:414-9|
|Yoshida, Takeshi; Song, Lanxi; Bai, Yun et al. (2016) ZEB1 Mediates Acquired Resistance to the Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer. PLoS One 11:e0147344|
|Ariyawutyakorn, Witthawat; Saichaemchan, Siriwimon; Varella-Garcia, Marileila (2016) Understanding and Targeting MET Signaling in Solid Tumors - Are We There Yet? J Cancer 7:633-49|
|Bunn Jr, Paul A; Minna, John D; Augustyn, Alexander et al. (2016) Small Cell Lung Cancer: Can Recent Advances in Biology and Molecular Biology Be Translated into Improved Outcomes? J Thorac Oncol 11:453-74|
|Helfrich, Barbara A; Kim, Jihye; Gao, Dexiang et al. (2016) Barasertib (AZD1152), a Small Molecule Aurora B Inhibitor, Inhibits the Growth of SCLC Cell Lines In Vitro and In Vivo. Mol Cancer Ther 15:2314-2322|
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