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 ...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.展开更多
Colorectal cancer(CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically(75%-80%), and only 20%-25% of patients have a family hist...Colorectal cancer(CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically(75%-80%), and only 20%-25% of patients have a family history.Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids(PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling,membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenome via modulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylationassociated CRC risk.展开更多
文摘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.
文摘Colorectal cancer(CRC) has been designated a major global problem, especially due to its high prevalence in developed countries. CRC mostly occurs sporadically(75%-80%), and only 20%-25% of patients have a family history.Several processes are involved in the development of CRC such as a combination of genetic and epigenetic alterations. Epigenetic changes, including DNA methylation play a vital role in the progression of CRC. Complex interactions between susceptibility genes and environmental factors, such as a diet and sedentary lifestyle, lead to the development of CRC. Clinical and experimental studies have confirmed the beneficial effects of dietary polyunsaturated fatty acids(PUFAs) in preventing CRC. From a mechanistic viewpoint, it has been suggested that PUFAs are pleiotropic agents that alter chromatin remodeling,membrane structure and downstream cell signaling. Moreover, PUFAs can alter the epigenome via modulation of DNA methylation. In this review, we summarize recent investigations linking PUFAs and DNA methylationassociated CRC risk.
