Molecular and therapeutic frontiers in anemia therapy

Anemia affects one-third of the population globally and is marked by impaired erythropoiesis that results in substantial mortality and morbidity. Over the past few decades, our understanding of the molecular mechanisms underlying anemia has progressed but translating that knowledge into effective targeted therapeutics remains challenging. Preclinical and clinical studies substantiate the efficacy of modulating erythropoietin-driven signaling pathways to stimulate erythropoiesis. Additional approaches include strategies to maintain iron homeostasis and control iron metabolism, using small molecules and oral supplements. New frontiers in molecular regulation of anemia include perturbation of regulatory genes and spliceosome proteins in erythroid cells, as well as mutation-specific therapeutic approaches. Finally, new evidence supporting the importance of neuronal signaling and mitochondrial dynamics in shaping erythropoiesis is pointing toward novel interventions. Here, we discuss the molecular and genetic factors underlying defective erythropoiesis and highlight current and emerging therapies, including molecular targets to overcome drug resistance.