Erythropoietin and Cancer: The Unintended Consequences of Anemia Correction

Abstract

Until 1990, erythropoietin (EPO) was considered to have a single biological purpose and action, the stimulation of red blood cell growth and differentiation. Slowly, scientific and medical opinion evolved, beginning with the discovery of an effect on endothelial cell growth in vitro and the identification of EPO receptors (EPORs) on neuronal cells. We now know that EPO is a pleiotropic growth factor that exhibits an anti-apoptotic action on numerous cells and tissues, including malignant ones. In this article, we present a short discussion of EPO, receptors involved in EPO signal transduction, and their action on non-hematopoietic cells. This is followed by a more detailed presentation of both pre-clinical and clinical data that demonstrate EPO’s action on cancer cells, as well as tumor angiogenesis and lymphangiogenesis. Clinical trials with reported adverse effects of chronic erythropoiesis-stimulating agents (ESAs) treatment as well as clinical studies exploring the prognostic significance of EPO and EPOR expression in cancer patients are reviewed. Finally, we address the use of EPO and other ESAs in cancer patients.

Systemic Lipopolysaccharide Administration-Induced Cognitive Impairments are Reversed by Erythropoietin Treatment in Mice

“…Those characteristics of EPO make it an attractive candidate for the treatment of SAE. However, those previous studies often used EPO with high doses and long-term exposure, which increase the risk of carcinogenesis and other possible side effects [5].…”

“…Erythropoietin (EPO) is a 34-kDa (165-amino acid) glycoprotein hematopoietic growth factor belonging to the type I cytokine superfamily, which has been used for the treatment of anemia as a result of many pathological causes, including cancer, prematurity, and renal insufficiency [5]. In addition to its known function in erythropoiesis, EPO has been reported to exert antiapoptotic, antiinflammatory, antioxidative, and neurotrophic properties [6].…”

Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats

“…Erythropoietin (EPO) is a 34-kDa (165-amino acid) glycoprotein hematopoietic growth factor, which has been used for the treatment of anemia resulting from many diseases, including cancer, prematurity, and renal insufficiency [7]. In addition to its known function in erythropoiesis, EPO posses antiinflammatory, antioxidative, and antiapoptotic properties [8][9][10][11][12].…”

A Systematic Review on the Erythropoietin Receptors Expression in Various Cancers and Importance of Recombinant Erythropoietin in Chemotherapy Induced Anaemia

“…61,62 At the same time these effect alter with tumour type as noted reduction in tumor growth with cisplatin and RHuEPO though couldn't produce similar effect with mitomycin C or cyclophosphamide. 63 McKinney et al 64 and Debeljak et al 65 proposed three possible theory mechanisms regarding tumor progression and reduces survival in some cancer types following RHuEPO therapy for cancer chemotherapy induced anemia. First due to local effects in tumour microenvironment affecting tumor cells or other as blood vessel endothelium and tumor-associated macrophages; second is direct or indirect systemic effect that impairs survival; third could be direct effect of EPO on stem cells leading to tumour progression and poor survival in some cancer patients.…”