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Strategies  \nChristopher A. Lucchesi 1,2, *, Demitria M. Vasilatis 1,3, Saisamkalpa Mantrala 1, Thenappan Chandrasekar 3, Maria Mudryj 1,4 and Paramita M. Ghosh 1,3,5, *  \nCitation: Lucchesi, C.A.; Vasilatis, D.M.; Mantrala, S.; Chandrasekar, T.; Mudryj, M.; Ghosh, P.M. Pesticides and Bladder Cancer: Mechanisms Leading to Anti-Cancer Drug Chemoresistance and New Chemosensitization Strategies. Int. J. Mol. Sci. 2023, 24, 11395. [https://](https://)  \n[doi.org/10.3390/ijms241411395](doi.org/10.3390/ijms241411395)[ ](doi.org/10.3390/ijms241411395)Academic Editors: Guilhem Bousquet and Melanie Di Benedetto  \nReceived: 25 May 2023  \nRevised: 5 July 2023  \nAccepted: 6 July 2023  \nPublished: 13 July 2023  \nCopyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 VA Northern California Health Care System, Mather, CA 95655, USA; [dvasilatis@ucdavis.edu](dvasilatis@ucdavis.edu) (D.M.V.); [mmudryj@ucdavis.edu](mmudryj@ucdavis.edu) (M.M.)  \n2 Department of Surgical & Radiological Sciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA  \n3 Department of Urological Surgery, School of Medicine, University of California Davis, Sacramento, CA 95817, USA  \n4 Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA 95616, USA  \n5 Department of Biochemistry and Molecular Medicine, School of Medicine, University of California Davis, Sacramento, CA 95817, USA  \n* Correspondence: [calucchesi@ucdavis.edu](calucchesi@ucdavis.edu) (C.A.L.); [paghosh@ucdavis.edu](paghosh@ucdavis.edu) (P.M.G.); Tel.: +1-916-734-7805 (P.M.G.)  \nAbstract: Multiple risk factors have been associated with bladder cancer. This review focuses on pesticide exposure, as it is not currently known whether agricultural products have a direct or indirect effect on bladder cancer, despite recent reports demonstrating a strong correlation. While it is known that pesticide exposure is associated with an increased risk of bladder cancer in humans and dogs, the mechanism(s) by which specific pesticides cause bladder cancer initiation or progression is unknown. In this narrative review, we discuss what is currently known about pesticide exposure and the link to bladder cancer. This review highlights multiple pathways modulated by pesticide exposure with direct links to bladder cancer oncogenesis/metastasis (MMP-2, TGF-􀀌, STAT3) and chemoresistance (drug efflux, DNA repair, and apoptosis resistance) and potential therapeutic tactics to counter these pesticide-induced affects.  \nKeywords: bladder cancer; pesticide exposure; metastasis  \n1. Introduction  \nIn the United States, approximately 82,290 people will be diagnosed with bladder cancer (BlCa) in 2023 [1] . California, which has the largest agricultural workforce, will seethe greatest increase in BlCa cases of all the states (8.8% of all BlCa in USA) [2] . Of these patients, almost three quarters will have non-muscle invasive BlCa (NMIBC) . Statistically, more than half of NMIBC will recur within 1 year after the first treatment and one third of cases will progress to muscle invasive BlCa (MIBC) [3] . Low-grade NMIBC is commonly managed with transurethral resection (TUR) with 5-year overall survival of 90%[4] . The 5-year survival for non-metastatic MIBC is 70%, which is in stark contrast to metastaticMIBC, which has a precipitous decrease in survival to 38% when regional and 6% when distant metastases are present. These data ultimately highlight the necessity to better understand BlCa progression [5] .  \nIn the developed world, ","cbCaiabGczPlccLB","https://ap.wps.com/l/cbCaiabGczPlccLB","pdf",3895226,22,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"What is the main focus of this narrative review?\",\"answer\":\"The review focuses on pesticide exposure and its link to bladder cancer, including how pesticides may contribute to initiation and progression.\"},{\"question\":\"Why are the mechanisms behind pesticide-related bladder cancer important?\",\"answer\":\"The specific mechanisms by which individual pesticides cause bladder cancer initiation or progression are unknown, and the review discusses what is currently known about the possible pathways.\"},{\"question\":\"Which chemoresistance-related processes are highlighted in the review?\",\"answer\":\"The review highlights chemoresistance pathways such as drug efflux, DNA repair, and apoptosis resistance, along with connections to oncogenesis and metastasis.\"}]","Pesticides and Bladder Cancer: Mechanisms Leading to Anti-Cancer Drug Chemoresistance and New Chemosensitization Strategies | PDF",1790234032,55]