Are erythropoietin receptors expressed in tumors? Facts and fiction--more careful studies are needed.

Journal of Clinical Oncology (Impact Factor: 17.88). 06/2007; 25(13):1813-4; author reply 1815. DOI: 10.1200/JCO.2006.09.7253
Source: PubMed
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    ABSTRACT: Erythropoietin (Epo) is an essential hormone that binds and activates the Epo receptor (EpoR) resident on the surface of erythroid progenitor cells, thereby promoting erythropoiesis. Recombinant human erythropoietin has been used successfully for over 20 years to treat anemia in millions of patients. In addition to erythropoiesis, Epo has also been reported to have other effects, such as tissue protection and promotion of tumor cell growth or survival. This became of significant concern in 2003, when some clinical trials in cancer patients reported increased tumor progression and worse survival outcomes in patients treated with erythropoiesis-stimulating agents (ESAs). One of the potential mechanisms proffered to explain the observed safety issues was that functional EpoR was expressed in tumors and/or endothelial cells, and that ESAs directly stimulated tumor growth and/or antagonized tumor ablative therapies. Since then, numerous groups have performed further research evaluating this potential mechanism with conflicting data and conclusions. Here, we review the biology of endogenous Epo and EpoR expression and function in erythropoiesis, and evaluate the evidence pertaining to the expression of EpoR on normal nonhematopoietic and tumor cells.
    Biologics: Targets & Therapy 06/2012; 6:163-89. DOI:10.2147/BTT.S32281
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    ABSTRACT: Gastric cancer has high prevalence and high modality worldwide. For many years, few improvements in the efficacy of treatments were reported for advanced gastric cancer settings. Although a novel molecular target agent trastuzumab, in combination with chemotherapy, prolongs overall survival time in advanced gastric cancer, resistance to this drug still exists among human epidermal growth factor receptor-2 (HER2) positive patients. HER2 and erythropoietin receptor (EPOR) downstream signaling pathway have some common factors like Akt, Erk and STATs. Also there exist evidences that EPOR may express on some solid tumors and probably promote tumor progression. So it is reasonable for us to hypothesis that HER2 and EPOR may be co-expressed in the same gastric cancer cell and if so, EPOR signaling pathway may overlaps that with HER2 and promotes HER2 induced signal transduction to cell proliferation. In clinical settings, a stimulation of EPOR will play antagonistic effects on trastuzumab-induced anti-tumor activity to HER2-positive gastric cancer patients. Co-expression of EPOR and HER2 is a predictive factor for resistance of trastuzumab in gastric cancer.
    Medical Hypotheses 09/2011; 77(6):948-52. DOI:10.1016/j.mehy.2011.07.021 · 1.15 Impact Factor
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    ABSTRACT: INTRODUCTION: Hypoxia induced radioresistance has been acknowledged for decades. One of the indirect evidences of the influence of hypoxia on radiation response comes from the observations of a correlation between tumor control and hemoglobin level. This review examines the clinical data on the prognostic and predictive role of hemoglobin level and hemoglobin manipulation in radiotherapy of squamous cell carcinomas of the head and neck, a tumor type where hypoxic radioresistance have been previously documented. THE INFLUENCE OF HEMOGLOBIN CONCENTRATION ON TUMOR OXYGENATION AND OUTCOME: The aim is to evaluate the existing literature for information of the influence of hemoglobin concentration and hemoglobin modifications on tumor oxygenation and outcome in head and neck squamous cell cancer patients. The data from several randomized trials show that while most studies have confirmed the prognostic value of hemoglobin, increasing the hemoglobin level through transfusion or erythropoietin stimulation did not result in improved outcome for patients with low initial hemoglobin levels. Clinical studies showed that smoking reduced the oxygen carrying capacity of the blood through formation of carboxyhemoglobin, and lead to poorer response to radiotherapy in smokers compared to non-smokers. Smoking also increased the risk of the development of secondary cancers. CONCLUSION AND FUTURE PERSPECTIVES: In conclusion, low hemoglobin is a significant negative prognostic factor for radiotherapy of head and neck cancer. Correction of pre-treatment low hemoglobin by blood transfusion and/or erythropoietin stimulating agents does, however, not improve the outcome. Smoking leads to a decrease in effective hemoglobin and poorer treatment outcome. Smoking should be avoided in order to improve the therapeutic efficacy of radiotherapy and development of other smoking-related diseases and/or secondary cancers.
    Acta oncologica (Stockholm, Sweden) 02/2012; 51(4):419-32. DOI:10.3109/0284186X.2011.653438 · 2.27 Impact Factor