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Cytotoxic Agents in the Era of Molecular Targets and Genomics

Massachusetts General Hospital, Boston, Massachusetts, USA

Correspondence: Bruce Chabner, M.D., Hematology/Oncology Associates, 100 Blossom Street, Cox 640, Boston, Massachusetts 02114-2617, USA. Telephone: 617-724-3200; Fax: 617-724-3166; e-mail: bchabner{at}partners.org

Cancer treatment is evolving due to the development of molecularly targeted agents and the utilization of pharmacogenomics and pharmacogenetics to identify patients who are at an increased risk for toxicity or may be uniquely responsive to cytotoxic therapies. By identifying polymorphisms in the human genome that confer changes in the ability to metabolize or activate cancer agents, a more patient-specific treatment approach can be initiated. Molecularly targeted therapies such as PS-341, flavopiridol, Iressa, and anti-vascular endothelial growth factor antibodies may help to overcome resistance to cytotoxic therapies by lowering the apoptotic threshold and increasing cytotoxicity. Using molecularly targeted agents in combination with traditional cytotoxic agents may increase the percentage of patients who achieve disease stabilization and prolonged survival. With the development of genetic tools and genotyping of tumor and patient prior to initiating treatment, antitumor efficacy may be increased with a substantial reduction in toxicity.

Key Words. Pharmacogenomics • Pharmacogenetics • Polymorphism • Molecular targeting

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