Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of microribonucleic acids

Sabeti Aghabozorgi, Amirsaeed and Moradi Sarabi, Mostafa and Jafarzadeh-Esfehani, Reza and Koochakkhani, Shabnaz (2020) Molecular determinants of response to 5-fluorouracil-based chemotherapy in colorectal cancer: The undisputable role of microribonucleic acids. World Journal of Gastrointestinal W J G O Oncology.

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Abstract

5-flurouracil (5-FU)-based chemotherapy is the main pharmacological therapy for advanced colorectal cancer (CRC). Despite significant progress in the treatment of CRC during the last decades, 5-FU drug resistance remains the most important cause of failure in CRC therapy. Resistance to 5-FU is a complex and multistep process. Different mechanisms including microsatellite instability, increased expression level of key enzyme thymidylate synthase and its polymorphism, increased level of 5-FU-activating enzymes and mutation of TP53 are proposed as the main determinants of resistance to 5-FU in CRC cells. Recently, microribonucleic acids (miRNA) and their alterations were found to have a crucial role in 5-FU resistance. In this regard, the miRNA-mediated mechanisms of 5-FU drug resistance reside among the new fields of pharmacogenetics of CRC drug response that has not been completely discovered. Identification of the biological markers that are related to response to 5-FU-based chemotherapy is an emerging field of precision medicine. This approach will have an important role in defining those patients who are most likely to benefit from 5-FU-based chemotherapy in the future. Thereby, the identification of 5-FU drug resistance mechanisms is an essential step to predict and eventually overcome resistance. In the present comprehensive review, we will summarize the latest knowledge regarding the molecular determinants of response to 5-FU-based chemotherapy in CRC by emphasizing the role of miRNAs.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine, Health and Life Sciences > School of Medicine
Depositing User: samira sepahvandy
Date Deposited: 04 Oct 2020 04:48
Last Modified: 04 Oct 2020 04:48
URI: http://eprints.lums.ac.ir/id/eprint/2380

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