This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, P. Articles by Weinshilboum, R. M. Search for Related Content PubMed PubMed Citation Articles by Yang, P. Articles by Weinshilboum, R. M.

Role of the Glutathione Metabolic Pathway in Lung Cancer Treatment and Prognosis: A Review

Ping Yang, Jon O. Ebbert, Zhifu Sun, Richard M. Weinshilboum

From the Division of Epidemiology and Cancer Center, Nicotine Dependence Center, Division of Primary Care Internal Medicine, and Department of Molecular Pharmacology and Experimental Therapeutics, Rochester, MN

Address reprint requests to Ping Yang, MD, PhD, Department of Health Sciences Research, Mayo Clinic Cancer Center, 200 First St. S.W., Charlton 6-261, Rochester, MN 55905; e-mail: yang.ping{at}mayo.edu

Inherent and acquired drug resistance is a cause of chemotherapy failure, and pharmacogenomic studies have begun to define gene variations responsible for varied drug metabolism, which influences drug efficacy. Platinum-based compounds are the most commonly used chemotherapeutic agents in the treatment of advanced stage lung cancer patients, and the glutathione metabolic pathway is directly involved in the detoxification or inactivation of platinum drugs. Consequently, genotypes corresponding to higher drug inactivation enzyme activity may predict poor treatment outcome. Available evidence is consistent with this hypothesis, although a definitive role for glutathione system genes in lung cancer prognosis needs to be elucidated. We present evidence supporting a role of the glutathione system in acquired and inherited drug resistance and/or adverse effects through the impact of either drug detoxification or drug inactivation, thus adversely effecting lung cancer treatment outcome. The potential application of glutathione system polymorphic genetic markers in identifying patients who may respond favorably, selecting effective antitumor drugs, and balancing drug efficacy and toxicity are discussed.

Supported by Grant No. NIH-CA84354 (Yang) from the U.S. National Cancer Institute and Mayo Foundation Funds.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

This article has been cited by other articles:

				J. Prousky The Treatment of Pulmonary Diseases and Respiratory-Related Conditions with Inhaled (Nebulized or Aerosolized) Glutathione Evid. Based Complement. Altern. Med., March 1, 2008; 5(1): 27 - 35. [Abstract] [Full Text] [PDF]

				R. Liu, P. E. Blower, A.-N. Pham, J. Fang, Z. Dai, C. Wise, B. Green, C. H. Teitel, B. Ning, W. Ling, et al. Cystine-Glutamate Transporter SLC7A11 Mediates Resistance to Geldanamycin but Not to 17-(Allylamino)-17-demethoxygeldanamycin Mol. Pharmacol., December 1, 2007; 72(6): 1637 - 1646. [Abstract] [Full Text] [PDF]

				B. Mukherjee, O. E. Salavaggione, L. L. Pelleymounter, I. Moon, B. W. Eckloff, D. J. Schaid, E. D. Wieben, and R. M. Weinshilboum GLUTATHIONE S-TRANSFERASE OMEGA 1 AND OMEGA 2 PHARMACOGENOMICS Drug Metab. Dispos., July 1, 2006; 34(7): 1237 - 1246. [Abstract] [Full Text] [PDF]