Microenvironment acidity as a major determinant of tumor chemoresistance: Proton pump inhibitors (PPIs) as a novel therapeutic approach

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
Sophie TaylorStefano Fais

Abstract

Despite the major progresses in biomedical research and the development of novel therapeutics and treatment strategies, cancer is still among the dominant causes of death worldwide. One of the crucial challenges in the clinical management of cancer is primary (intrinsic) and secondary (acquired) resistance to both conventional and targeted chemotherapeutics. Multiple mechanisms have been identifiedthat underlie intrinsic and acquired chemoresistance: these include impaired drug uptake, increased drug efflux, deletion of receptors, altered drug metabolism, quantitative and qualitative alterations in drug targets, increased DNA damage repair and various mechanisms of anti-apoptosis. The fast efflux of anticancer drugs mediated by multidrug efflux pumps and the partial or complete reversibility of chemoresistance combined with the absence of genetic mutations suggests a multifactorial process. However, a growing body of recent evidence suggests that chemoresistance is often triggered by the highly acidic microenvironment of tumors. The vast majority of drugs, including conventional chemotherapeutics and more recent biological agents, are weak bases that are quickly protonated and neutralized in acidic environments, such as the ext...Continue Reading

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Citations

May 9, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Wirginia LikusMarek J Łos
Nov 26, 2015·Journal of Translational Medicine·Stefano Fais
May 18, 2016·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Xing-Dong XiongJin-Ming Yang
May 5, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Cristina FedericiStefano Fais
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Jan 18, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Simonetta AstigianoOttavia Barbieri
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Feb 5, 2019·Cancer Metastasis Reviews·Mariantonia LogozziStefano Fais
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Dec 19, 2019·Expert Opinion on Therapeutic Patents·Enrico Pierluigi Spugnini, Stefano Fais
Jun 17, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Huarui ZhangAiping Lu
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Dec 4, 2019·Journal of Enzyme Inhibition and Medicinal Chemistry·Mariantonia LogozziStefano Fais
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Aug 11, 2020·Journal of Drug Targeting·Sepideh NezhadiFarid Dorkoosh
Aug 9, 2020·Cancer Management and Research·Huining TianGuixia Wang
Sep 6, 2018·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Ran Hong, Song Iy Han
Aug 6, 2020·International Journal of Molecular Sciences·Stefano BurgioCeleste Caruso Bavisotto
Dec 14, 2018·International Journal of Molecular Sciences·Enrico Pierluigi SpugniniStefano Fais
Apr 4, 2019·Frontiers in Oncology·Catherine Vander Linden, Cyril Corbet

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