Targeting Stress Erythropoiesis Pathways in Cancer

Abstract

Cancer-related anemia (CRA) is a common multifactorial disorder that adversely affects the quality of life and overall prognosis in patients with cancer. Safety concerns associated with the most common CRA treatment options, including intravenous iron therapy and erythropoietic-stimulating agents, have often resulted in no or suboptimal anemia management for many cancer patients. Chronic anemia creates a vital need to restore normal erythropoietic output and therefore activates the mechanisms of stress erythropoiesis (SE). A growing body of evidence demonstrates that bone morphogenetic protein 4 (BMP4) signaling, along with glucocorticoids, erythropoietin, stem cell factor, growth differentiation factor 15 (GDF15) and hypoxia-inducible factors, plays a pivotal role in SE. Nevertheless, a chronic state of SE may lead to ineffective erythropoiesis, characterized by the expansion of erythroid progenitor pool, that largely fails to differentiate and give rise to mature red blood cells, further aggravating CRA. In this review, we summarize the current state of knowledge on the emerging roles for stress erythroid progenitors and activated SE pathways in tumor progression, highlighting the urgent need to suppress ineffective erythropoiesis in cancer patients and develop an optimal treatment strategy as well as a personalized approach to CRA management.

Effect of Chemotherapy on hs- C Reactive Protein, Some Blood Picture and Kidney Function in Patients With Neuroblastoma

“…Cancer patients frequently develop anemia, either as a result of a tumor-driven blood disorder or as a side effect of chemotherapy. Whereas the antineoplastic therapy itself may be a significant contributor to anemia or conversely, may make the patients' pre-existing anemia worse [23].…”

Signaling networks guiding erythropoiesis

“…The significance of the link between JAK (Janus kinase) and MAP kinase signaling in erythropoiesis lies in the involvement of both pathways in its regulation [14,15]. The combined action of EPO and stem cell factor SCF leads to the activation of MAP kinases, specifically ERK1/2, which plays a crucial role in promoting increased erythropoiesis [16,17]. Moreover, it has been established that the JAK-STAT pathway plays a significant role in the process of erythropoiesis, specifically in regulating the erythroid progenitor cells throughout their developmental stages [18].…”

Interplay between stress and cancer—A focus on inflammation

“…Chronic stress considerably affects hematopoietic stem/progenitor cells ( Heidt et al, 2014 ; Vignjević Petrinović et al, 2020 ; Barrett et al, 2021 ) and mature immune cells, altering the hematopoietic homeostasis and dysregulating both innate and adaptive immune responses ( Dhabhar, 2014 ). In general, different populations of hematopoietic cells within tumor microenvironment such as: myeloid-derived suppressor cells, tumor-associated macrophages (M2 polarized), polymorphonuclear cells, type 2 and 3 of innate lymphoid cells, mast cells, regulatory T cells, and nucleated erythroid cells are considered to exert the immunosuppressive effects, whereas tumor-infiltrating lymphocytes, dendritic cells and natural killer cells are associated with an anti-tumor activity ( Salemme et al, 2021 ; Vignjević Petrinović et al, 2022 ). Thus, chronic stress can promote cancer progression by accumulating the immune cells that exert immunosuppressive effects ( An et al, 2021 ) as well as suppressing the number and function of immunoprotective cells ( Dhabhar, 2014 ).…”

“…Frontiers in Physiology frontiersin.org lymphoid cells, mast cells, regulatory T cells, and nucleated erythroid cells are considered to exert the immunosuppressive effects, whereas tumor-infiltrating lymphocytes, dendritic cells and natural killer cells are associated with an anti-tumor activity (Salemme et al, 2021;Vignjević Petrinović et al, 2022). Thus, chronic stress can promote cancer progression by accumulating the immune cells that exert immunosuppressive effects as well as suppressing the number and function of immunoprotective cells (Dhabhar, 2014).…”