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Project

Visible Light-Controlled Combination Strategy for Treating Nonmuscle Invasive Bladder Cancers

Funder: Congressionally Directed Medical Research Programs

Funding period
USD 592 K
Funding amount
Abstract
PUBLIC ABSTRACT

This proposed project aims to address the critical issue of bladder cancer, one of the Fiscal Year 2016 Peer Reviewed Cancer Research Program Topic Areas. This application is seeking a solution for more effective treatment for the most diagnosed types of bladder cancers. The proposed study responds to both of the Military Relevance Focus Areas: military-relevant risk factors associated with cancer, and gaps in cancer prevention, early detection/diagnosis, and treatment that have a particularly profound impact on the health and well-being of military Service members, Veterans, and their beneficiaries.



Bladder cancer is the fourth most common cancer in men. Seventy to 80 percent of bladder cancers are diagnosed at early stages and are treated by surgery under cystoscopy. Due to the high rate of recurrence after surgery, adjuvant therapies, such as intravesical chemotherapy and BCG (Bacillus Calmette–Guérin) vaccine, are used. However, recurrence, progression, and side effects remain important problems that make bladder cancer one of the most expensive cancers to treat. More effective and selective treatment options are direly needed.



We are developing a unique, visible light-based strategy to effectively and selectively treat early-stage bladder cancers by taking advantage of both the formation of protoporphyrin IX (a special compound used for fluorescence imaging and treatment) selectively in cancer cells and our new light-activatable prodrug (an inactive form of a drug that is changed to a drug inside the body with light). We expect that our prodrug will be effectively activated by cancer cell-specific protoporphyrin IX-based photodynamic therapy (PDT, a US Food and Drug Administration [FDA]-approved photochemistry-based light treatment), and thus greatly improve therapeutic efficacy with minimal damage to the bladder. Our long-term goal is to advance this combination strategy to clinical translation. The objective of this proposed work is to prove our concept using prodrugs of clinically available anticancer drugs in both in vitro (cultured cancer cells) and in vivo (animal) models. Specifically, a bladder cancer model made in rat bladder will be used to better mimic the physiology of human bladder cancers.



Our approach is expected to improve therapeutic efficacy and minimize side effects by using a unique and innovative combination strategy. Protoporphyrin IX will first be selectively formed in cancer cells, following the FDA-approved protocol for fluorescence cystoscopic detection (looking inside the bladder using a fluorescent dye). Non-toxic prodrug will be localized to mitochondria of cells. Then, the prodrug will be selectively activated in cancer cells by illumination with visible light. This new combination will be a valuable treatment option for bladder cancers that are resistant to current standard adjuvant therapies, like chemotherapy and BCG.



The proposed study aims to fill the gaps in prevention of cancer recurrence and treatment that have a particularly profound impact on the health of military members, Veterans, and their beneficiaries. Bladder cancer is the fourth most common type in US Veterans. Smoking is the leading risk factor for bladder cancer. The prevalence of smoking is much higher in Veterans (27%) than in non-Veterans (21%). Older Veterans who are cigarette smokers are at much higher risk for bladder cancers. In a recent report in Veterans and Agent Orange: Update 2014, bladder cancer was moved from “inadequate or insufficient” to “limited or suggestive” evidence of association. Based on the report from the US Department of Veterans Affairs, bladder cancer is one of the known adverse health conditions for those who were exposed to drinking water contaminated with industrial solvents, including benzene, at the US Marine Corps Base Camp at Lejeune, NC, from the 1950s to the 1980s.

 
1,001
Projects
USD 453.8 M
Aggregated funding amount
USD 599 K
Average funding amount
Project list item
Intravesical delivery of an Fc-enhanced CD40 agonist antibody for the treatment of bladder cancer

Bladder Cancer Advocacy Network to Jeffrey Ravetch, David Knorr

USD 300,000
2020 - 2022
Project list item
Epigenetic regulators of subtype plasticity in bladder cancer

Bladder Cancer Advocacy Network to John Robert Christin

USD 1,700
2020 - 2020
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Characterization of Nectin-4 expression in molecular subtypes of urothelial cancer and mechanisms of resistance to enfortumab vedotin

Bladder Cancer Advocacy Network to Carissa Ellen Chu

USD 1,700
2020 - 2020
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Recombinant CCL2 as a novel treatment strategy for bladder cancer

Bladder Cancer Advocacy Network to Neelam Mukherjee, Robert Scott Svatek

USD 50,000
2020 - 2021
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Defining NRF2 induced tumor invasion in bladder cancer

Bladder Cancer Advocacy Network to Yuki Kita, William Youngkwan Kim, Bernard Weissman

USD 50,000
2020 - 2021
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Targeting regulatory B cells (Bregs) to improve anti-bladder cancer immunity

Bladder Cancer Advocacy Network to Burles Avner Johnson, David McConkey

USD 50,000
2020 - 2021
Project list item
Alpha1H: A Unique Bladder Cancer Therapeutic, Acting with Great Precision

European Commission

USD 2,452,885
2020 - 2022
Project list item
Dissecting myeloid cell-mediated resistance to immune checkpoint blockade in bladder cancer

National Cancer Institute to NINA BHARDWAJ, JUN ZHU, MATTHEW GALSKY

USD 703,400
2020 - 2025
Project list item
SGLT-2 Inhibitors and Early Bladder Cancer Events: An International Multi-Centre Study

Canadian Institutes of Health Research to Elisabetta Patorno, Laurent Azoulay, Devin Abrahami, Lysanne Campeau, Blanaid Hicks, Robert William Platt, Sebastian Schneeweiss, Oriana Hoi Yun Yu

USD 88,269
2020 - 2022
Project list item
Implication of neutrophil extracellular traps in the efficacy of bladder-sparing therapy in muscle invasive bladder cancer

Canadian Institutes of Health Research to Wassim Kassouf, Ciriaco A. Piccirillo, Jonathan David Spicer

USD 138,878
2020 - 2025
Project list item
Chimeric RNAs and their implication in lymphatic metastasis of bladder cancer

National Cancer Institute to HUI LI

USD 205,913
2020 - 2025
Project list item
CD40 agonism for the treatment of bladder cancer

National Cancer Institute to CHRISTOPHER STUART GARRIS

USD 64,554
2020 - 2023
Project list item
Effect of APOBEC3 on Bladder Cancer Biology and Response to Immunotherapy

National Cancer Institute to ANDREW TRUONG

USD 45,016
2020 - 2023
Project list item
Analysis of the effect of IDO inhibition on activation of the aryl hydrocarbon receptor pathway in bladder cancer

São Paulo Research Foundation to Humberto Dellê

 
2020 - 2021
Project list item
A new bladder cancer model based on tissue reprogramming and gene targeting

National Cancer Institute to FLAMINIA TALOS, DAIFENG WANG

USD 203,843
2020 - 2021
Project list item
Identification and analysis of early prognostic markers of bladder cancer using generated nanobodies

Russian Science Foundation to Sergei Tillib

 
2020 - 2022
Project list item
Roles of epigenetic regulators in bladder cancer progression

University of California - Cancer Research Coordinating Committee to Zhu Wang

USD 74,960
2020 - 2020
Project list item
Platform Selection for Biomarker Directed Radiotherapy for Bladder Cancer

NIHR Evaluation Trials and Studies Coordinating Centre to Catharine West

USD 51,871
2020 - 2020
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