RESEARCH - Pharmacogenetics of folate-related drug targets in cancer treatment

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Summary

Pharmacogenomics

Oct 2005, Vol. 6, No. 7, Pages 673-689

Pharmacogenetics of folate-related drug targets in cancer treatment

Kim Robien, ­Alanna Boynton & ­Cornelia M Ulrich

1Fred Hutchinson Cancer Research Center, Cancer Prevention Program, 1100

Fairview Ave N, M4-B402, Seattle, WA 98109 1024, USA. nulrich@...

2University of Washington, Department of Epidemiology, Seattle, WA 98195,

USA

3University of Washington, Interdisciplinary Graduate Program in Nutritional

Sciences, Seattle, WA 98195, USA

Folate metabolism is the target of two major drug groups: folate antagonists

(for example, methotrexate) and thymidylate synthase inhibitors (for

example, 5-fluorouracil). These agents are used in the treatment of cancer,

as well as for other conditions, such as rheumatoid arthritis. High-dose

cancer treatment protocols can induce a state of acute folate depletion

which may lead to significant treatment-related toxicity. Polymorphisms in

folate-metabolizing enzymes may modify the therapeutic effectiveness and

toxicity of these drugs. This review briefly summarizes the drugs targeting

the folate pathway and describes common polymorphisms in folate-metabolizing

enzymes and transport proteins. Pharmacogenetic studies investigating

folate-related drug targets in the treatment of colorectal cancers and

hematologic malignancies will subsequently be discussed. Findings to date

illustrate a potential for targeting therapy based on patients' genotypes,

in order to improve outcomes and reduce toxicity. However, larger,

well-designed studies are needed to confirm these early findings.

http://www.futuremedicine.com/doi/abs/10.2217/14622416.6.7.673

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