Principal Investigators:
Thea Pugatsch PhD, Chaim Lotan MD, Herzl Schwalb PhD

Collaboration
Roche

Abstract

A particularly aggressive form of breast cancer leading to rapid metastasis is characterized by the over-expression of the HER-2(erbB2)-protein on the surface of malignant cells. The most effective treatment for the close to a third of affected women, who are found to be HER-2 positive, is the administration of Herceptin (recombinant humanized anti-HER-2 monoclonal antibody). Herceptin acts by blocking erbB-2, a cognate receptor of neuregulins. Binding of erbB-2 to neuregulins has been shown to be involved in the promotion, survival and growth of cardiac myocytes in mice and rats in both postnatal and adult hearts. As one of the serious side effects of this therapy is the development of cardiac dysfunction, it is conceivable that administration of Herceptin leads to the interruption of the pathway involved in the myocardial adaptation to physiologic stress and injury. In this study we intend to analyze the cardiotoxic action of Herceptin in vitro on isolated neonatal and adult rat cardiac myocytes and on isolated perfused rat hearts and at a later stage in the clinic in Israeli patients. Results may allow an insight into the process that leads to the severe side effects of this otherwise highly beneficial treatment.

Status
Funded