The Neuregulin-1/erbB Signaling Activities with focus on the Susceptibility of the Heart to Anthracycline-based Therapeutics

VASTI C, HERTIG CM

World Journal of Cardiology

Baishideng Publishing Group Inc

Lugar: Pleasanton; Año: 2014

1949-8462

he neuregulin (NRG1) signaling pathway was revealed essential for cardiac morphogenesis by the phenotype of genetically recombined mouse mutated in the nrg1 or either cognate receptors erbb2 or erbb4 genes. Since then, the components and the activities displayed by this pathway have been progressively identified. The clinical impact of the NRG1 pathway was the evidence of the increase incidence of dilated cardiomyopathies in patients undergoing the combined treatment with anthracyclines and trastuzumab, a humanized antibody against the oncogenic erbB2. It has been suggested that a deficient NRG1 signaling sensitizes the heart to anthracycline toxicity in a potentiated manner. It is, therefore, expected that relevant pathways would be synergistically affected under this condition. The oxidative stress-induced apoptosis is a highly accepted mechanism in the literature for the loss of cardiomyocytes in doxorubicin-treated hearts. Although this pathway may affect cardiac remodeling in a s