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5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future
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SYSNO ASEP 0536981 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title 5-fluorouracil and other fluoropyrimidines in colorectal cancer: Past, present and future Author(s) Vodenková, Soňa (UEM-P) ORCID, RID
Buchler, T. (CZ)
Červená, Tereza (UEM-P) ORCID, RID
Veškrnová, V. (CZ)
Vodička, Pavel (UEM-P) RID
Vymetálková, Veronika (UEM-P) RIDArticle number 107447 Source Title Pharmacology and Therapeutics. - : Elsevier - ISSN 0163-7258
Roč. 206, feb. (2020)Number of pages 19 s. Language eng - English Country GB - United Kingdom Keywords colorectal cancer ; 5-fluorouracil ; 5-fluorouracil pro-drugs Subject RIV FR - Pharmacology ; Medidal Chemistry OECD category Pharmacology and pharmacy R&D Projects NV17-30920A GA MZd - Ministry of Health (MZ) NV19-09-00237 GA MZd - Ministry of Health (MZ) Method of publishing Limited access Institutional support UEM-P - RVO:68378041 UT WOS 000509737600009 EID SCOPUS 85075856144 DOI 10.1016/j.pharmthera.2019.107447 Annotation 5-Fluorouracil (5-FU) is an essential component of systemic chemotherapy for colorectal cancer (CRC) in the palliative and adjuvant settings. Over the past four decades, several modulation strategies including the implementation of 5-FU-based combination regimens and 5-FU pro-drugs have been developed and tested to increase the anti-tumor activity of 5-FU and to overcome the clinical resistance.
Despite the encouraging progress in CRC therapy to date, the patients response rates to therapy continue to remain low and the patients benefit from 5-FU-based therapy is frequently compromised by the development of chemoresistance. Inter-individual differences in the treatment response in CRC patients may originate in the unique genetic and epigenetic make-up of each individual.
The critical element in the current trend of personalized medicine is the proper comprehension of causes and mechanisms contributing to the low or lack of sensitivity of tumor tissue to 5-FU-based therapy. The identification and validation of predictive biomarkers for existing 5-FU-based and new targeted therapies for CRC treatment will likely improve patients' outcomes in the future.
Herein we present a comprehensive review summarizing options of CRC treatment and the mechanisms of 5-FU action at the molecular level, including both anabolic' and catabolic ways. The main part of this review comprises the currently known molecular mechanisms underlying the chemoresistance in CRC patients. We also focus on various 5-FU pro-drugs developed to increase the amount of circulating 5-FU and to limit toxicity. Finally, we propose future directions of personalized CRC therapy according to the latest published evidence.Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2021 Electronic address https://www.sciencedirect.com/science/article/abs/pii/S0163725819301998?via%3Dihub
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