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5-Fluorouracil: mechanisms of action and clinical strategies

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TLDR
This work has shown that novel genes identified in DNA microarray profiling have the potential to identify novel genes that are involved in mediating resistance to 5-FU, and these genes might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to5-FU-based chemotherapy.
Abstract
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 might prove to be therapeutically valuable as new targets for chemotherapy, or as predictive biomarkers of response to 5-FU-based chemotherapy.

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Journal ArticleDOI

Cancer drug resistance: an evolving paradigm

TL;DR: There are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.
Journal ArticleDOI

Modulation of oxidative stress as an anticancer strategy.

TL;DR: The controversial role of ROS in tumour development and in responses to anticancer therapies is addressed, and the idea that targeting the antioxidant capacity of tumour cells can have a positive therapeutic impact is elaborate.
Journal ArticleDOI

Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction

TL;DR: Evidence is presented for a large class of non-oncogenes that are essential for cancer cell survival and present attractive drug targets and theoretical considerations for combining orthogonal cancer therapies are provided.
Journal ArticleDOI

Molecular mechanisms of drug resistance

TL;DR: The signalling pathways involved in regulating tumour cell response to chemotherapy more completely than ever before are characterized, which will facilitate the future development of rational combined chemotherapy regimens, in which the newer targeted therapies are used in combination with cytotoxic drugs to enhance chemotherapy activity.
References
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Journal ArticleDOI

p53, guardian of the genome

Journal Article

Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo

TL;DR: It is demonstrated that a temperature-sensitive p53 induces temperature-dependent decreases in the expression of the apoptosis-suppressing gene bcl-2 in the murine leukemia cell M1, while simultaneously stimulating increases in theexpression of bax, a gene which encodes a dominant-inhibitor of the Bcl-1 protein.
Journal ArticleDOI

A gene expression database for the molecular pharmacology of cancer

TL;DR: Gene-drug relationships for the clinical agents 5-fluorouracil and L-asparaginase exemplify how variations in the transcript levels of particular genes relate to mechanisms of drug sensitivity and resistance.
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