From initiation to promotion and to the development of an invasive phenotype, a series of molecular changes contribute to those aberrations and puts the entire airway epithelium of smokers at a greater risk for lung cancer. Our central hypothesis is that a subset of specific molecular aberrations discovered in pre-invasive lesions and from the airway epithelium of high-risk individuals is directly involved in the development of lung cancer, and that derivation of a signature composed of these functionally significant alterations in at-risk individuals will represent a powerful biomarker for risk as well as an intermediate endpoint biomarker of response to chemoprevention therapy. To test this hypothesis, we propose to use two separate approaches to interrogate the field of carcinogenesis.
In aim 1 we will study the biological relevance of candidate biomarkers derived from the analysis of preinvasive lesions obtained in the current cycle of funding.
In aim 2 we will refine a gene expression signature derived from the bronchial epithelial cells from the large airways by stratifying the population further and integrating data from state of the art genomic and proteomic analyses in specimens obtained from the same individuals.
In aim 3, we will test the candidates from aims 1 and 2 in preinvasive lesions from bronchial epithelial cells for risk assessment and as intermediate endpoint biomarkers of chemoprevention therapy. The studies proposed are highly novel in their focus on functionally relevant biomarkers, the testing for biomarkers that track with the disease risk, and the application of multiple cutting edge technologies. These studies will further our understanding of the functional role of our candidate biomarkers in lung cancer development, refine a molecular signature of risk in large airway epithelial cells and test those in high-risk cohorts for new molecular diagnostic and intermediate endpoint biomarker of response to chemoprevention.
Molecular strategies are being tested to determine whether it improves the assessment of risk for lung cancer. We hypothesize that a subset of molecular aberrations in the airways of high risk individuals are involved in the development of lung cancer, and that such aberrations will represent a powerful biomarker for risk as well as an intermediate endpoint biomarker of response to chemoprevention therapy.
|Boutaud, Olivier; Sosa, I Romina; Amin, Taneem et al. (2016) Inhibition of the Biosynthesis of Prostaglandin E2 By Low-Dose Aspirin: Implications for Adenocarcinoma Metastasis. Cancer Prev Res (Phila) 9:855-865|
|Hassanein, Mohamed; Hight, Matthew R; Buck, Jason R et al. (2016) Preclinical Evaluation of 4-[18F]Fluoroglutamine PET to Assess ASCT2 Expression in Lung Cancer. Mol Imaging Biol 18:18-23|
|Hassanein, Mohamed; Qian, Jun; Hoeksema, Megan D et al. (2015) Targeting SLC1a5-mediated glutamine dependence in non-small cell lung cancer. Int J Cancer 137:1587-97|
|Qian, Jun; Hassanein, Mohamed; Hoeksema, Megan D et al. (2015) The RNA binding protein FXR1 is a new driver in the 3q26-29 amplicon and predicts poor prognosis in human cancers. Proc Natl Acad Sci U S A 112:3469-74|
|Harris, Fredrick T; Rahman, S M Jamshedur; Hassanein, Mohamed et al. (2014) Acyl-coenzyme A-binding protein regulates Beta-oxidation required for growth and survival of non-small cell lung cancer. Cancer Prev Res (Phila) 7:748-57|
|Sekhar, Konjeti R; Benamar, Mouadh; Venkateswaran, Amudhan et al. (2014) Targeting nucleophosmin 1 represents a rational strategy for radiation sensitization. Int J Radiat Oncol Biol Phys 89:1106-14|
|Hassanein, Mohamed; Hoeksema, Megan D; Shiota, Masakazu et al. (2013) SLC1A5 mediates glutamine transport required for lung cancer cell growth and survival. Clin Cancer Res 19:560-70|
|Wang, Jing; Qian, Jun; Hoeksema, Megan D et al. (2013) Integrative genomics analysis identifies candidate drivers at 3q26-29 amplicon in squamous cell carcinoma of the lung. Clin Cancer Res 19:5580-90|
|Nagathihalli, Nagaraj S; Massion, Pierre P; Gonzalez, Adriana L et al. (2012) Smoking induces epithelial-to-mesenchymal transition in non-small cell lung cancer through HDAC-mediated downregulation of E-cadherin. Mol Cancer Ther 11:2362-72|
|Hassanein, Mohamed; Callison, J Clay; Callaway-Lane, Carol et al. (2012) The state of molecular biomarkers for the early detection of lung cancer. Cancer Prev Res (Phila) 5:992-1006|
Showing the most recent 10 out of 25 publications