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

Abstract

Erythropoietin (EPO) is the primary and influential mediator of red cell synthesis. Its action is mediated by various pathways as JAK2-STAT5, Ras-Raf-MAP kinase, PI-3K-Akt and protein kinase C and adaptor protein CrkL following interaction between EPO and erythropoietin receptors (EPOR) in the various cells. Apart from erythropoiesis it also regulates neuronal functioning and angiogenesis etc. Nevertheless, the pathological presence of these EPOR receptors is seen in various tumour cells that have raised concerns regarding enhanced tumour growth and impaired overall survival.

Targeting Stress Erythropoiesis Pathways in Cancer

“…Hypoxia-inducible EPO signaling has been suggested to play a significant role in cancer’s aggressive behavior and drug resistance ( Acs et al, 2003 ; Miyake et al, 2013 ). Although EPORs expression has been demonstrated in different tumor tissues ( Kumar et al, 2017 ), the critical issues regarding the specificity of the commercially available anti-EPOR antibodies for immunohistochemistry have been raised and therefore a consensus on both the expression and potential functional significance of EPORs in cancer cells has not been reached so far ( Bennett et al, 2016 ). Several studies showed that many investigations relying on detection of the EPOR were not reproducible because of the antibody issues and pointed towards the widespread use of nonspecific anti-EPOR antibodies that provide false positive staining with tissues as a main reason for the conflicting data on EPOR protein expression ( Elliott et al, 2012 ; Elliott et al, 2013 ).…”

Chemotherapy-induced anemia: etiology, pathophysiology, and implications for contemporary practice

“…7 Erythropoiesis stimulating agents in CIA Erythropoietin (EPO) was initially identified in 1906 and is a circulatory hematopoietic glycoprotein hormone that facilitates erythrocyte production. 68 EPO is expressed by renal and hepatic interstitial cells and is upregulated in the setting of hypoxia to stimulate erythrocyte production in the bone marrow. 68,69 Following secretion by the liver and kidneys, EPO binds to erythroid precursor cells to induce both maturation and differentiation.…”

“…68 EPO is expressed by renal and hepatic interstitial cells and is upregulated in the setting of hypoxia to stimulate erythrocyte production in the bone marrow. 68,69 Following secretion by the liver and kidneys, EPO binds to erythroid precursor cells to induce both maturation and differentiation. 68 ESAs are a class of recombinant medications that induce red cell proliferation via utilization of iron stores that are necessary for effective erythropoiesis.…”

“…68,69 Following secretion by the liver and kidneys, EPO binds to erythroid precursor cells to induce both maturation and differentiation. 68 ESAs are a class of recombinant medications that induce red cell proliferation via utilization of iron stores that are necessary for effective erythropoiesis. 67 ESAs are categorized by their duration of action and are divided into short-acting (epoetin alfa, epoetin zeta, epoetin beta, and epoetin theta) and long-acting (darbepoetin alfa) ESAs.…”