The
hormone erythropoietin (EPO) is essential for the survival, proliferation and differentiation of the erythrocytic progenitors. The EPO receptor (EPO-R) of erythrocytic cells belongs to the
cytokine class I receptor family and signals through various
protein kinases and
STAT transcription factors. The EPO-R is also expressed in many organs outside the bone marrow, suggesting that EPO is a pleiotropic anti-apoptotic factor. The controversial issue as to whether the EPO-R is functional in
tumor tissue is critically reviewed. Importantly, most studies of EPO-R detection in
tumor tissue have provided falsely positive results because of the lack of EPO-R specific
antibodies. However, endogenous EPO appears to be necessary to maintain the viability of endothelial cells and to promote
tumor angiogenesis. Although there is no clinical proof that the administration of
erythropoiesis stimulating agents (ESAs) promotes
tumor growth and mortality, present recommendations are that (i) ESAs should be administered at the lowest dose sufficient to avoid the need for
red blood cell transfusions, (ii) ESAs should not be used in patients with active malignant disease not receiving
chemotherapy or
radiotherapy, (iii) ESAs should be discontinued following the completion of a
chemotherapy course, (iv) the target Hb should be 12 g/dL and not higher and (v) the risks of shortened survival and
tumor progression have not been excluded when ESAs are dosed to target Hb <12 g/dL.