The overarching goal of the project is to develop a population risk-stratification tool that will allow efficacious and cost-effective lung cancer screening. Lung cancer represents an ideal malignancy for screening because of its prevalence, identifiable risk groups (current/former smokers) and ability to surgically cure the disease if diagnosed early. However, there are no robust screening techniques with options such as CT scans fraught with cost and harm from large numbers of false positives. One attractive approach is to exploit field carcinogenesis, the concept that the same genetic/environmental milieu that results in a lesion in one area of the lung will impact upon the entire aerodigestive mucosa. The buccal (cheek) mucosa is a """"""""molecular mirror"""""""" of lung carcinogenesis, although current techniques are inadequate to translate this phenomenon into a minimally intrusive screening test. Our preliminary data show that the alteration of nanoscale architecture in buccal cells is exquisitely sensitive to field carcinogenesis and, hence, may serve as a robust biomarker for lung cancer. These nanoarchitectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy. In this study, we will refine PWS technology, develop a prediction rule based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. We will validate our preliminary data that there is no confounding with regards to demographics, risk factors (e.g. smoking intensity) and non-lung primary cancers. Finally, we will prospectively validate buccal PWS in a case control and a cohort studies. This project will provide the requisite data for future definitive large scale multicenter validation trials that could unequivocally prove the efficacy of buccal PWS analysis as the first line of screening for lung cancer allowing rational use of more expensive or intrusive tools such as CT scans or bronchoscopy. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.

Public Health Relevance

No existing technique allows accurate and cost-effective lung cancer screening. This project will lead towards development of a minimally invasive optical technique that would enable lung cancer screening in asymptomatic population by a simple cheek swap that can be performed in a primary care setting.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA155284-01
Application #
8025856
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Baker, Houston
Project Start
2011-09-26
Project End
2015-07-31
Budget Start
2011-09-26
Budget End
2012-07-31
Support Year
1
Fiscal Year
2011
Total Cost
$605,317
Indirect Cost
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
Stephens, Andrew D; Liu, Patrick Z; Banigan, Edward J et al. (2018) Chromatin histone modifications and rigidity affect nuclear morphology independent of lamins. Mol Biol Cell 29:220-233
Gladstein, Scott; Damania, Dhwanil; Almassalha, Luay M et al. (2018) Correlating colorectal cancer risk with field carcinogenesis progression using partial wave spectroscopic microscopy. Cancer Med 7:2109-2120
Almassalha, L M; Tiwari, A; Ruhoff, P T et al. (2017) The Global Relationship between Chromatin Physical Topology, Fractal Structure, and Gene Expression. Sci Rep 7:41061
Chandler, John E; Stypula-Cyrus, Yolanda; Almassalha, Luay et al. (2017) Colocalization of cellular nanostructure using confocal fluorescence and partial wave spectroscopy. J Biophotonics 10:377-384
Li, Yue; Zhang, Di; Capoglu, Ilker et al. (2017) Measuring the Autocorrelation Function of Nanoscale Three-Dimensional Density Distribution in Individual Cells Using Scanning Transmission Electron Microscopy, Atomic Force Microscopy, and a New Deconvolution Algorithm. Microsc Microanal 23:661-667
Bauer, Greta M; Stypula-Cyrus, Yolanda; Subramanian, Hariharan et al. (2017) The transformation of the nuclear nanoarchitecture in human field carcinogenesis. Future Sci OA 3:FSO206
Cherkezyan, Lusik; Zhang, Di; Subramanian, Hariharan et al. (2017) Review of interferometric spectroscopy of scattered light for the quantification of subdiffractional structure of biomaterials. J Biomed Opt 22:30901
Cherkezyan, Lusik; Zhang, Di; Subramanian, Hariharan et al. (2016) Reconstruction of explicit structural properties at the nanoscale via spectroscopic microscopy. J Biomed Opt 21:25007
Almassalha, Luay M; Bauer, Greta M; Chandler, John E et al. (2016) The Greater Genomic Landscape: The Heterogeneous Evolution of Cancer. Cancer Res 76:5605-5609
Almassalha, Luay M; Bauer, Greta M; Chandler, John E et al. (2016) Label-free imaging of the native, living cellular nanoarchitecture using partial-wave spectroscopic microscopy. Proc Natl Acad Sci U S A 113:E6372-E6381

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