Preclinical and clinical studies: a preview of potential future applications of erythropoietic agents

Understanding the tissue distribution of erythropoietin receptors and cellular actions of erythropoietic agents may facilitate the development of wider applications for these compounds. Erythropoietin receptors have been identified in the central nervous system (CNS), retina, heart, vascular endothelium, kidney, lung, liver, gastrointestinal and reproductive tracts, and erythroid bone marrow precursors. Potential benefits of erythropoietic agents in several therapeutic areas may result from actions other than hematopoiesis stimulation. Their hematopoietic effects may also have broader applications in treating anemia of the elderly and non-chemotherapy (CT)-related anemia in patients with cancer. Furthermore, because hypoxic tumor cells tend to be more resistant to radiation therapy (RT) and some forms of CT, and more aggressive than normoxic cells, increased oxygenation resulting from anemia correction may increase RT and CT sensitivity, possibly impacting treatment outcomes. However, clinical studies addressing this hypothesis have conflicting results. Preliminary evidence suggests erythropoietin has CNS neuroprotective effects, including potential clinical benefits in ischemic stroke. In addition, data suggest that erythropoietin (epoetin alfa) may attenuate declines in cognitive function during CT for early-stage breast cancer. Erythropoietin may have benefits in retinal disease, peripheral neuropathy, and myocardial ischemia. Thus, accumulating evidence suggests that erythropoietic agents may have clinical utility outside CT-related anemia.