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Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update
- Source :
- Cellular Oncology. 43:989-1001
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Colorectal cancer (CRC) is a disease with high morbidity and mortality rates. 5-fluorouracil (5-FU) is the first-line recommended drug for chemotherapy in patients with CRC, and it has a good effect on a variety of other solid tumors as well. Unfortunately, however, due to the emergence of drug resistance the effectiveness of treatment may be greatly reduced. In the past decade, major progress has been made in the field of 5-FU drug resistance in terms of molecular mechanisms, pre-clinical (animal) models and clinical trials. In this article we systematically review and update current knowledge on 5-FU pharmacogenomics related to drug uptake and activation, the expression and activity of target enzymes (DPD, TS and MTHFR) and key signaling pathways in CRC. Furthermore, a summary of drug combination strategies aimed at targeting specific genes and/or pathways to reverse 5-FU resistance is provided. Based on this, we suggest that causal relationships between genes, pathways and drug sensitivity should be systematically considered from a multidimensional perspective. In the design of research methods, emerging technologies such as CRISPR-Cas, TALENS and patient-derived xenograft models should be applied as far as possible to improve the accuracy of clinically relevant results.
- Subjects :
- 0301 basic medicine
Drug
Oncology
Cancer Research
medicine.medical_specialty
Colorectal cancer
media_common.quotation_subject
Disease
Drug resistance
03 medical and health sciences
0302 clinical medicine
Internal medicine
Autophagy
Animals
Humans
Medicine
media_common
biology
business.industry
General Medicine
medicine.disease
Clinical trial
030104 developmental biology
Drug Resistance, Neoplasm
Pharmacogenetics
Fluorouracil
030220 oncology & carcinogenesis
Pharmacogenomics
Methylenetetrahydrofolate reductase
biology.protein
Molecular Medicine
Colorectal Neoplasms
business
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 22113436 and 22113428
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Cellular Oncology
- Accession number :
- edsair.doi.dedup.....428ae9a5998d71e13fad2c5380fca557