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Erythropoietin and its receptor in breast cancer: Putting together the pieces of the puzzle

Department of Biomolecular Sciences, Section of Clinical Biochemistry, University Carlo Bo, Urbino, Italy.
The Oncologist (Impact Factor: 4.54). 08/2008; 13(7):761-8. DOI: 10.1634/theoncologist.2008-0110
Source: PubMed

ABSTRACT The expression of erythropoietin (Epo) and the Epo receptor (EpoR) has been detected in healthy tissue as well as in a variety of human cancers, including breast. Functional Epo/EpoR signaling in cancer cells, which contributes to disease initiation/progression, is not completely straightforward and is difficult to reconcile with the clinical practice of preventing/treating anemia in cancer patients with recombinant Epo. Preclinical and clinical investigations have provided contrasting results, ranging from a beneficial role that improves the patient's overall survival to a negative impact that promotes tumor growth progression. A careful gathering of Epo/EpoR biomolecular information enabled us to assemble an unexpected jigsaw puzzle which, via distinct JAK-dependent and JAK-independent mechanisms and different internalization/recycling as well as ubiquitination/degradation pathways, could explain most of the controversies of preclinical and clinical studies. However, until the mechanisms of the contrasting literature data are resolved, this new point of view may shed light on the Epo/EpoR paracrine/autocrine system and function, providing a basis for further studies in order to achieve the highest possible benefit for cancer patients.

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    • "Thus, cells can circumvent JAK2-dependent pathway for the JAK2-independent pathway (ERK1/2). Mannello and other previously reported about a JAK2-independent pathway [60]. "
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    • "The recent debate about Epo/EpoR axis in cancer (in particular in BC patients treated with Epo for cancer related anaemia) [33] has raised the need, on one side to understand the presence and function of EpoR on cancer cells [30], and on the other to take into consideration that Epo may impair, not improve, BC survival [10]. A hypothetical bio-molecular mechanism regulating Epo/EpoR axis in BC has been theorized [41], trying to explain the diverse biological availability of activated or cleaved EpoR with endogenous/exogenous Epo in breast microenvironment, which may in such condition either promote tumor proliferation or patient survival in BC. Until such time as the mechanisms of the contrasting literature data are resolved, the use and risks of Epo therapy should be carefully weighed, balancing the potential beneficial effects ameliorating anaemia against the detrimental tumor promoting ac- tivity. "
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