5-Fluorouracil: mechanisms of action and clinical strategies

@article{Longley20035FluorouracilMO,
  title={5-Fluorouracil: mechanisms of action and clinical strategies},
  author={Daniel B. Longley and Denis Paul Harkin and Patrick Gerard Johnston},
  journal={Nature Reviews Cancer},
  year={2003},
  volume={3},
  pages={330-338}
}
5-Fluorouracil (5-FU) is widely used in the treatment of cancer. Over the past 20 years, increased understanding of the mechanism of action of 5-FU has led to the development of strategies that increase its anticancer activity. Despite these advances, drug resistance remains a significant limitation to the clinical use of 5-FU. Emerging technologies, such as DNA microarray profiling, have the potential to identify novel genes that are involved in mediating resistance to 5-FU. Such target genes… 

5-Fluorouracil: Mechanisms of Resistance and Reversal Strategies

The purpose of this work is to review the published studies on the mechanisms of action and resistance of 5-fluorouracil and procedures for the identification of new genes involved in resistance with microarray techniques.

Modulation of Reactive Oxygen Species to Overcome 5-Fluorouracil Resistance

This review summarizes selected compounds and endogenous cellular targets modulating ROS generation to overcome 5-FU resistance.

5-Fluorouracil: identification of novel downstream mediators of tumour response.

The potential of microarray analysis to identify novel genes associated with response or resistance to chemotherapeutic agents is demonstrated, including spermine/spermidine acetyl transferase and annexin II, which have not been linked to 5-FU response.

Identifying new targets for cancer drug 5′-fluorouracil

A novel systematic approach to identify new targets of 5′-Fluorouracil (5-FU) and suggests a novel way to target chromatin defects using 5-FU, which is of clinical significance as chromatin regulatory factors and histone modifiers are frequently mutated in human cancer.

5-Fluorouracil: A Narrative Review on the Role of Regulatory Mechanisms in Driving Resistance to This Chemotherapeutic Agent

The function of non-coding transcripts in the modulation of response of neoplastic cells to 5-FU is provided and there is an increasing interest in targeting these transcripts in various kinds of cancers that are treated by5-FU.

The combination of curcumin and 5-fluorouracil in cancer therapy

Curcumin has been found to be able to negatively regulate some molecules and genes in cancer cells that are related to the chemoresistance and sensitivity of cancer cells to 5-FU.

Epigenetic reversal of acquired resistance to 5-fluorouracil treatment

Treatment of bolus 5-FU-resistant colorectal cancer cells with low-dose 5-azadeoxycytidine (DAC), an inhibitor of DNA hypermethylation, restored sensitivity to 5-fu as well as 5-fluorouridine, and overcame resistance to bolus 4-FU.

Signaling Pathways Involved in 5-FU Drug Resistance in Cancer

How the function of 5-fluorouracil in JAK/STAT, Wnt, Notch, NF-κB, and hedgehogs in some cancers is discussed.
...

References

SHOWING 1-10 OF 118 REFERENCES

Clinical Pharmacology of 5-Fluorouracil

Summary5-Fluorouracil, first introduced as a rationally synthesised anticancer agent 30 years ago, continues to be widely used in the management of several common malignancies including cancer of the

Capecitabine: a novel agent for the treatment of solid tumors

Clinical trials have shown that capecitabine is an effective, well-tolerated treatment for breast and colorectal cancer, with response rates of 20-26% in anthracycline- and taxane-pretreated metastatic breast cancer and 30% in metastatic Breast cancer.

A review of the pharmacology and clinical activity of new chemotherapy agents for the treatment of colorectal cancer.

  • A. Adjei
  • Biology, Medicine
    British journal of clinical pharmacology
  • 1999
Attempts at identifying more effective chemotherapeutic agents for colorectal cancer have yielded oral formulations and prodrugs of 5-fluorouracil with apparently equivalent efficacy, and the topoisomerase I inhibitors represent a new class of agents with a novel mechanism of action.

Identification of 5-fluorouracil-inducible target genes using cDNA microarray profiling.

DNA microarray technology is used to identify genes that are transcriptionally activated by 5-FU treatment in the MCF-7 breast cancer cell line and demonstrate the potential of DNA microarrays to identify novel genes involved in mediating the response of tumor cells to chemotherapy.

Preferential activation of capecitabine in tumor following oral administration to colorectal cancer patients

Capecitabine is a novel fluoropyrimidine carbamate rationally designed to generate 5-fluorouracil preferentially in tumors, which is explained to a great extent by the activity of TP in colorectal tumor tissue, (the enzyme responsible for the conversion of 5′-DFUR to 5-FU), which is approximately four times that in adjacent healthy tissue.

Sequential methotrexate and 5-fluorouracil: mechanisms of synergy.

In mice bearing the sarcoma 180 tumor, pretreatment with MTX results in synergy, providing an understanding of the MTX/5-FU synergy that has been well documented in several experimental systems.

Attenuation of the antitumor activity of 5-fluorouracil by (R)-5-fluoro-5,6-dihydrouracil.

Testing the effects of (R)-5-fluoro-5,6-dihydrouracil (5-FUH2), the 5-FU catabolite extensively formed in the absence of 5-EU, on the antitumor activity and toxicity of 4-EU-treated rats bearing large s.c. tumors found it to be similar to the toxicity produced by 7-11% transient weight loss.

Oxaliplatin: mechanism of action and antineoplastic activity.

A decreased likelihood of resistance development makes oxaliplatin a good candidate for first-line therapy and studies also demonstrate additive and/or synergistic activity with a number of other compounds, however, suggesting the possible use of oxali Platin in combination therapies.

Enhancement of 5-fluorouracil's anticancer activity by dipyridamole.

Thymidylate synthase pharmacogenetics in colorectal cancer.

Prospective confirmation of the impact of TSER on outcome, after TS-targeted chemotherapy, will define the utility of pharmacogenetics to optimize the selection of 5-FU therapy for colorectal cancer.
...