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New Insights Into Erythropoietin and Epoetin Alfa: Mechanisms of Action, Target Tissues, and Clinical Applications

The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

Correspondence: Mitchell J. Weiss, M.D., The Children’s Hospital of Philadelphia, 316B Abramson Research Building, Philadelphia, Pennsylvania 19104, USA. Telephone: 215-590-0565; Fax: 215-590-4834; e-mail: weissmi{at}email.chop.edu

Recombinant human erythropoietin (epoetin alfa) has proven beneficial for the treatment of various anemias. The mechanism of action of endogenous erythropoietin and the therapeutic use of epoetin alfa to stimulate red blood cell production and improve the quality of life in cancer patients are reviewed here. Epoetin alfa may also attenuate the cognitive dysfunction associated with cancer therapy. Interestingly, functional endogenous erythropoietin receptor signaling pathways have been demonstrated in numerous nonerythropoietic tissues. Of particular importance, epoetin alfa confers neurotrophic and neuroprotective effects in cultured neurons and in several animal models for neurologic disease. In one clinical trial, epoetin alfa appeared to limit functional and histologic damage in patients with stroke. Therefore, in cancer patients receiving chemotherapy, the beneficial effects of epoetin alfa could be mediated not only through enhanced erythrocyte production but also via direct effects on the nervous system. Further investigation into the nonerythropoietic effects of epoetin alfa could broaden its clinical utility for patients with cancer and also provide new therapies for various neurologic disorders.

Key Words. Erythropoietin • Signal transduction • Epoetin alfa • Anemia • Cancer • Central nervous system • Apoptosis

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