The role of erythropoietin and erythropoietin receptor expression in breast cancer

Erythropoietin (EPO) plays a number of important functions in the body. Contrary to original beliefs, its activity is not limited to exerting effects on cells along the erythropoietic pathway. Newly published results continue to provide information on novel functions of the protein in other types of tissues, as well as on the important roles played by EPO in pathological processes. With no doubt, EPO has a significant impact on the biology of breast cancer cells by affecting cells’ proliferation, apoptosis, resistance to chemotherapy, as well as expression of various types of receptors. EPO exerts its direct action on breast cancer stem-like cells by activation of specific signaling pathways responsible for protection of the tumor from chemotherapy and accelerating disease progression. EPO could inhibit chemotherapeutic drug-induced apoptosis and cytotoxicity. Its correlation with tissue hypoxia may play a significant role in the therapeutic resistance of hypoxic tumors. In recent years, the role of endogenous EPO in regulation of carcinogenesis was also noted. Exogenous EPO, in the form of rhEPO, had been introduced with best intention to treat patients with cancer-related anemia in the course of breast cancer. While it decreases the transfusion requirements and improves the quality of life of cancer patients, randomized trials have demonstrated that rhEPO administration is associated with shorter progression-free and overall survival. Observations allow also to say that EPO antagonizes treatment with the anti-HER2 antibody trastuzumab by activating EpoR/JAK2 downstream effectors, effectively bypassing HER2 signaling. Although increasing amount of information is available regarding the role of EPO and EpoR in breast cancer, elucidation of the activity and involvement of these proteins in complex processes occurring within the cancer cells requires extensive research. Every set of results being published answers some of the questions while instead raise new ones.

Breast neoplasms; Erythropoietin; Hypoxia

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