Erythropoietin in cancer: the new face of an old friend.

During the last decade, anemia, a very common situation in patients with malignant diseases, either associated with chemotherapy or not, is being treated with recombinant erythropoietin (rEPO). Recent experimental findings have elucidated the role of EPO as a strongly anti-apoptotic agent in multiple non-erythroid and neoplastic tissues. The discovery of probably functional EPO receptors (EPOR) on malignant cells, hinting that EPO may act as a tumor growth factor, raised embarrassing thoughts regarding the routine administration of erythropoiesis-stimulating agents (ESAs). In addition, the results of a few clinical trials showing a negative impact on overall survival of rEPO-treated cancer patients, although strongly criticized for several methodological pitfalls, led the FDA to force a "black label" warning concerning the use of rEPO and to recommend that physicians should use the lowest possible dose of ESAs in chemotherapy-treated cancer patients. This recommendation comes in accord with the recent guidelines of European Organisation for Research and Treatment of Cancer (EORTC) which are reviewed in this paper, along with the structure of EPO and EPOR, the role of EPO on normal and malignant cells and the clinical applications of EPO.