Neuregulin in heart failure : reverse translation from cancer cardiotoxicity to new heart failure therapy.

Trastuzumab is a monoclonal antibody to the ErbB2 (Her2nue) receptor over-expressed in Her2(+) breast cancer. Trastuzumab-related cardiotoxicity has revealed the importance of ErbB2 signaling in the heart. Neuregulin (NRG-1) is an important stress-mediated paracrine growth factor that signals through the family of ErbB receptors to promote cardioprotection (myocyte cell survival, proliferation, differentiation, hypertrophy, and angiogenesis). Animal models with disrupted NRG/ErbB signaling fail to develop normally or result in impaired cardiac function post-natally. Pre-clinical animal studies and early-phase human studies suggest that recombinant NRG-1 holds promise as a new therapy for the treatment of various forms of heart failure. Much work is needed to further understand the exact mechanisms of cardiac repair and to find a safe mode of application for recombinant NRG-1 in heart failure.