Recombinant human erythropoietin therapy in patients with cancer: efficacy, risks and the controversy of EpoR expression

Recombinant human erythropoietin (rHuEpo) is widely used to treat anaemia in patients with cancer. Concerns regarding its safety arose from early experimental studies suggesting erythropoietin receptor (EpoR) expression in tumour cells and potential pro-tumorigenic effects. However, many of these findings were generated using non-specific antibodies or incomplete molecular validation, leading to uncertainty about the clinical relevance of EpoR in oncology. A structured narrative review was conducted through a PubMed/MEDLINE search (1990–2025) using predefined terms related to EpoR and cancer. Additional references were identified via citation tracking. Studies evaluating EpoR expression in tumour-derived cell lines or human tumour tissues or exploring the clinical implications of rHuEpo therapy were included. A bibliometric analysis was also performed to contextualize historical trends in publication volume. Early studies reported widespread EpoR expression in cancer models; however, most used non-validated polyclonal antibodies and lacked molecular confirmation. When more rigorous approaches were adopted, EpoR detection in tumours was inconsistent or negligible. Clinical trials reporting adverse outcomes with rHuEpo were largely conducted before current regulatory restrictions, used variable haemoglobin targets or enrolled patients who would not be eligible for treatment today. Current evidence does not support a biologically meaningful role of EpoR in solid tumours. When used within approved indications and modern safety guidance, rHuEpo has not been consistently associated with tumour progression or reduced survival. Continued methodological rigour is essential to clarify remaining uncertainties and optimize rHuEpo use in oncology.