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Identify the DNA Adduct and Associated Metabolic Alterations in Bladder Cancer of Smokers

Funder: National Cancer Institute

Funding period
USD 1.2 M
Funding amount
Project Summary/Abstract Smoking is a major risk factor for bladder cancer (BCa). Patients with current or past history of smoking have a three times higher likelihood of developing BCa. Smoking is also known to have a potential dose-dependent effect on the grade and stage of BCa, with high-dose smokers having more aggressive disease. In addition, smokers with BCa have a higher likelihood of failing chemotherapy. Currently, markers that can stratify smokers based on their risk of developing BCa are lacking. Furthermore, predictive markers for aggressive BCa among high-dose smokers are also lacking. The central goal of this application is to characterize the DNA adducts and biochemical alterations observed in smoking-associated BCa and use this information to develop metabolite-based predictive markers and therapeutic strategies for this deadly disease. Cigarette smoke contains a number of xenobiotic compounds that include arylamines, methylated metabolites, Nicotine- derived nitrosamine ketone (NNK), Benzo[a]pyrene (BaP), nicotine etc which are usually metabolized by the xenobiotic metabolism and excreted in the urine. Our strong preliminary data demonstrates altered DNA adducts and reprogramming of xenobiotic metabolism in BCa smokers. This effect is exaggerated by components of cigarette smoke including nicotine. Using a novel metabolomics approach, we had earlier shown that BCa was associated with a unique metabolic signature. From the patients perspective it is important to be able to measure these markers non-invasively in body fluids like urine. Intriguingly, metabolites are the end products of overall cellular metabolism. These are small molecules that could be easily monitored in body fluids to interrogate disease phenotype in question. Quiet provocatively, our group is being established to utilize metabolites to further monitor tumors. Thus, our current proposal aims to identify DNA adducts and associated metabolites in BCa smokers and use the information to develop markers for early identification of patients who are at risk for developing aggressive bladder cancer. Further will enable clinicians to take an informed decision about more appropriate therapeutic strategies towards personalized medicine.

USD 51.2 M
Aggregated funding amount
USD 1.5 M
Average funding amount
Project list item
DNA adductome of human bladder from the tobacco exposome

National Institute of Environmental Health Sciences to ROBERT J. TURESKY

USD 922,448
2019 - 2023
Project list item
Targeting TAM (Tyro3-Axl-Mer) family of transmembrane receptor tyrosine kinases in bladder cancer.

Bladder Cancer Advocacy Network to Arpita Roy

USD 1,700
2018 - 2018
Project list item
Novel Biomarkers for the Clinical Management of Bladder Cancer

National Cancer Institute to VINATA B LOKESHWAR

USD 902,622
2018 - 2023
Project list item
Subtyping Bladder Cancer: A Multi-omic, Exposure-informed, Genealogical Approach (MErGE)

National Cancer Institute to HEIDI ANNE HANSON

USD 298,810
2018 - 2023
Project list item
New Drug and Technology Assessment in Bladder Cancer: Creation of a Novel Canadian Policy Model for Bladder Cancer

Canadian Institutes of Health Research to Murray Dale Krahn, Girish Satish Kulkarni, William Wai Lun Wong, George Andrew Tomlinson, Nathan Perlis, Wassim Kassouf, Peter Colin Black, Shabbir Muhammad Husayn Alibhai

USD 77,161
2018 - 2019
Project list item
Potentiation of Immunotherapy with targeted nanoporphyrin in bladder cancer

United States Department of Veterans Affairs to CHONG-XIAN PAN

2018 - 2022
Project list item
Positive Loop of Smoking and Extracellular Vesicles in Bladder Field Cancerization

Congressionally Directed Medical Research Programs to Yifen Lee

USD 616,000
2017 - 2018
Project list item
Precision Cotargeting Tumor and Its Microenvironment in Bladder Cancer

Congressionally Directed Medical Research Programs to Hungming Lam

USD 706,000
2017 - 2018
Project list item
Delivery of Targeting Nano-Photo-Imiquimod to Enhance Response Rate of Advanced Bladder Cancer to Check Point Blockade Antibody Therapy

Congressionally Directed Medical Research Programs to Kit S Lam

USD 4,634,675
2017 - 2018
Project list item
Translation of a Clinical Molecular Diagnostic Assay for Bladder Cancer

National Cancer Institute to STEVE GOODISON

USD 1,823,874
2017 - 2022
Project list item
Racial Disparity in Bladder Cancer and Identification of Altered Metabolism in African American Compare to European Bladder Cancer

National Cancer Institute to NAGIREDDY PUTLURI

USD 1,086,461
2017 - 2022
Project list item
Development of Novel Noninvasive Tests for Prognostic Predictions for Bladder Cancer

Congressionally Directed Medical Research Programs to Vinata B Lokeshwar

USD 608,000
2016 - 2017
Project list item
Sh3gl2 and chemosensitivity of bladder cancer

National Cancer Institute to ROSALYN M ADAM

USD 492,035
2016 - 2019
Project list item

National Cancer Institute to CHARLES J ROSSER

USD 3,471,615
2016 - 2021
Project list item
A potential role of aberrant DNA methylation in the chemoresistance in bladder cancer cells

Japan Society for the Promotion of Science to Naoya MASUMORI, Tetsuya Shindo, Naotaka NISHIYAMA, 信雄 新海

USD 41,190
2016 - 2019
Project list item
Regulation of Urinary Bladder Carcinogenesis and Progression by SPARC

National Cancer Institute to NEVEEN SAID

USD 1,726,720
2016 - 2020
Project list item
Dose-response modeling of 3-nitrobenzanthrone-induced alterations of the energy metabolism in urothelial cells

German Research Foundation to Simone Schmitz-Spanke

2016 - 2019
Project list item
Visible Light-Controlled Combination Strategy for Treating Nonmuscle Invasive Bladder Cancers

Congressionally Directed Medical Research Programs to Kelly Standifer

USD 592,000
2015 - 2016
Project list item
Gender Difference in Bladder Cancer Susceptibility

National Cancer Institute to XUE SEAN LI

USD 423,201
2015 - 2017
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