Grant Number:	5R01CA225002-05 Interpret this number
Primary Investigator:	Backman, Vadim
Organization:	Northwestern University
Project Title:	Translating Buccal Nanocytology for Lung Cancer Screening Into Clinical Practice
Fiscal Year:	2022

Project Summary The overarching goal of the Academic Industrial Partnership grant 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 low-dose CT (LDCT) scans fraught with cost and harm from large numbers of false positives. In order to make lung cancer screening viable, it is imperative to develop a test to pre-screen for LDCT by identifying the subset of patients who are likely to harbor lung cancers and would benefit from LDCT. The test must be sensitive to early disease (e.g. Stage I), low-cost, and able to be carried out in a primary care setting. The goal of this project is to develop such a test. 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 aero digestive 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. The 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 nano-architectural changes can be detected in a practical and highly accurate fashion via a novel biophotonics technology, partial wave spectroscopic (PWS) microscopy (“nanocytology”). In this study, PWS technology will be refined and a prediction rule developed based on the PWS-detectable nanoscale alterations that is optimized for early stage, curable lung cancer. The goal of the proposed project is to finalize the remaining technology development aspects to translate nanocytology into a practical, accurate, and low- cost test, bring it to the point where it is viable for population screening, and conduct a pre-definitive clinical validation. The team envision that upon completion of this project, nanocytology will be ready for a definitive clinical trial leading to a launch in clinical practice. This novel paradigm could transform the clinical practice of lung cancer screening and thereby mitigate the large toll of this malignancy in Americans.




Leveraging chromatin packing domains to target chemoevasion in vivo.
Authors: Frederick J. , Virk R.K.A. , Ye I.C. , Almassalha L.M. , Wodarcyk G.M. , VanDerway D. , Carrillo Gonzalez P. , Nap R.J. , Agrawal V. , Anthony N.M. , et al. .
Source: Biorxiv : The Preprint Server For Biology, 2024-11-15 00:00:00.0; , .
EPub date: 2024-11-15 00:00:00.0.
PMID: 39605341
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Authors: Nap R.J. , Gonzalez P.C. , Coraor A.E. , Virk R.K.A. , de Pablo J. , Backman V. , Szleifer I. .
Source: Biorxiv : The Preprint Server For Biology, 2024-11-12 00:00:00.0; , .
EPub date: 2024-11-12 00:00:00.0.
PMID: 39605663
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Authors: Flowerday E. , Daneshkhah A. , Su Y. , Backman V. , Goldstein S.D. .
Source: Journal Of Biophotonics, 2024-11-11 00:00:00.0; , p. e202400273.
EPub date: 2024-11-11 00:00:00.0.
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Source: Elife, 2024-09-27 00:00:00.0; 13, .
EPub date: 2024-09-27 00:00:00.0.
PMID: 39331520
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Authors: Alom S. , Daneshkhah A. , Acosta N. , Anthony N. , Liwag E.P. , Backman V. , Gaire S.K. .
Source: Biorxiv : The Preprint Server For Biology, 2024-08-21 00:00:00.0; , .
EPub date: 2024-08-21 00:00:00.0.
PMID: 39229026
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Authors: Gaire S.K. , Daneshkhah A. , Flowerday E. , Gong R. , Frederick J. , Backman V. .
Source: Journal Of Biomedical Optics, 2024 Jun; 29(6), p. 066501.
EPub date: 2024-05-24 00:00:00.0.
PMID: 38799979
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Authors: Kant A. , Guo Z. , Vinayak V. , Neguembor M.V. , Li W.S. , Agrawal V. , Pujadas E. , Almassalha L. , Backman V. , Lakadamyali M. , et al. .
Source: Nature Communications, 2024-05-21 00:00:00.0; 15(1), p. 4338.
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Authors: Chang A. , Prabhala S. , Daneshkhah A. , Lin J. , Subramanian H. , Roy H.K. , Backman V. .
Source: Scientific Reports, 2024-04-02 00:00:00.0; 14(1), p. 7808.
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PMID: 38565871
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Source: Cell Reports, 2024-03-26 00:00:00.0; 43(3), p. 113897.
EPub date: 2024-03-16 00:00:00.0.
PMID: 38493478
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Authors: Carignano M. , Kröger M. , Almassalha L.M. , Agrawal V. , Li W.S. , Pujadas-Liwag E.M. , Nap R.J. , Backman V. , Szleifer I. .
Source: Arxiv, 2024-03-05 00:00:00.0; , .
EPub date: 2024-03-05 00:00:00.0.
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Source: Plos One, 2024; 19(5), p. e0301000.
EPub date: 2024-05-28 00:00:00.0.
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Source: Medrxiv : The Preprint Server For Health Sciences, 2023-10-31 00:00:00.0; , .
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Source: Research Square, 2023-10-31 00:00:00.0; , .
EPub date: 2023-10-31 00:00:00.0.
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Source: Research Square, 2023-10-17 00:00:00.0; , .
EPub date: 2023-10-17 00:00:00.0.
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Source: Scientific Reports, 2023-08-22 00:00:00.0; 13(1), p. 13702.
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Source: Acs Central Science, 2023-06-28 00:00:00.0; 9(6), p. 1200-1212.
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Source: Frontiers In Cell And Developmental Biology, 2023; 11, p. 1293891.
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Source: Science Advances, 2021 01; 7(1), .
EPub date: 2021-01-01 00:00:00.0.
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Source: Aging Clinical And Experimental Research, 2020 Oct; 32(10), p. 2141-2158.
EPub date: 2020-09-02 00:00:00.0.
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Authors: Eid A. , Eshein A. , Li Y. , Virk R. , Van Derway D. , Zhang D. , Taflove A. , Backman V. .
Source: Optics Letters, 2020-09-01 00:00:00.0; 45(17), p. 4810-4813.
PMID: 32870863
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Source: Science Advances, 2020 01; 6(2), p. eaax6232.
EPub date: 2020-01-08 00:00:00.0.
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Authors: Huang K. , Li Y. , Shim A.R. , Virk R.K.A. , Agrawal V. , Eshein A. , Nap R.J. , Almassalha L.M. , Backman V. , Szleifer I. .
Source: Science Advances, 2020 Jan; 6(2), p. eaay4055.
EPub date: 2020-01-10 00:00:00.0.
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Authors: Gladstein S. , Almassalha L.M. , Cherkezyan L. , Chandler J.E. , Eshein A. , Eid A. , Zhang D. , Wu W. , Bauer G.M. , Stephens A.D. , et al. .
Source: Nature Communications, 2019-04-10 00:00:00.0; 10(1), p. 1652.
EPub date: 2019-04-10 00:00:00.0.
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