Evidence for erythropoietin as a molecular targeting agent.
Erythropoietin, in its standard role for the treatment of anemia, is often mechanistically regarded simply as increasing blood oxygen-carrying capacity and hence decreasing tumor hypoxia. In reality, erythropoietin (a member of the cytokine superfamily) is expressed in a multitude of tissues/cell types including erythroid and cancer cells, and the liver and central nervous system. Erythropoietin expression is induced by hypoxia-inducible factor-1, which itself is induced during hypoxia. Whereas it has no endogenous tyrosine kinase activity of its own, erythropoietin, via constitutively associated JAK2, can activate several signaling pathways including STAT5, RAS, and phosphoinositol 3-kinase. An increased understanding of these pathways is already opening up new clinical indications, particularly in terms of oncology and neurology. Current arrays/molecular endpoint studies in clinical trials should identify key components of the particular signaling pathways that will guide further use in the development of both better synergistic therapies as well as new molecular targets.
Department of Oncology, McGill University, Montreal, Canada.
Brian
B
Leyland-Jones
D000740:Anemia / Q000188:drug therapy* / Q000209:etiology; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy*; D020411:Oligonucleotide Array Sequence Analysis; D017467:Receptors, Erythropoietin / Q000378:metabolism; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000502:physiology
D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin