EPO is the hormone, normally produced by kidneys, that promotes erythropoiesis, or red blood cell production. A recombinant form of this hormone is used as a breakthrough treatment for patients suffering from end-stage kidney disease and anaemia. Despite its vast therapeutic efficacy, EPO and its derivatives, epoetins, are suspected to impact cancer growth and increase the risk of cardiovascular disease. The EU-funded project EPOCAN (Gaining sage on the Epoetins' saga: assessing long term risks and advancing towards better Epoetin driven treatment modalities) aimed to resolve these safety concerns. It addressed the effect of EPO on tumour progression and thromboembolic events in cancer patients. For patients with chronic kidney disease the increased risk of cardiovascular disease and cancer was estimated. Scientists found no connection between EPO and thromboembolic events. In patients with acute myocardial infarction, high doses of EPO did not cause pro-inflammatory changes. However, resistance to EPO-stimulating agents (ESAs) was associated with increased mortality in patients undergoing dialysis. ESAs had a hypertensive effect, and patients treated with high ESA dose showed increased risk of mortality. The animal models developed during the project helped to better understand the role of EPO in cancer. Overexpression of EPO led to a later onset of tumour formation, suggesting that EPO might be anti-tumorigenic – before a tumour is formed. However, after the tumour was formed, EPO promoted its growth. Accordingly, tumour xenograft models carrying human breast and lung cancer cell lines showed that EPO stimulated lung cancer cell growth and affected their metastatic potential. Important research and potential clinical anti-EPO receptor antibody tools were generated by EPOCAN. It is expected that they will be of extreme value for determining the presence of EPO receptors on human tumour samples and by that aid in the decision making process of whether or not to treat individual cancer patients with epoetins. EPOCAN generated important understanding of major adverse events caused by EPO treatment, such as the increased mortality of patients treated with high ESA dose. Nevertheless, it was demonstrated that EPO has no direct effects on platelet function. Knowing the EPO-associated health risks will help formulate the necessary regulatory schemes for EPO use, leading to safer outcomes.
Erythropoietin, tumour, thromboembolic, cancer, cardiovascular, antibodies