Introduction

The invention demonstrates that, in rats and cancer patients, anthracyclines (i.e. doxorubicin), cardiotoxic anticancer drugs, can reduce the plasma levels of chromogranin A (CgA), an endogenous cardioprotective protein, and that systemic administration of low-dose exogenous CgA can restore cardioprotection in rats. This suggests a cardioprotective role and a diagnostic/prognostic value of CgA.

Technical features

Results of the present invention demonstrate, on one hand, that systemic administration of low-dose exogenous CgA to rats can prevent anthracyclines-induced cardiotoxicity, by reducing systemic damage and by inhibiting myocardial inflammation, apoptosis, fibrosis, oxidative stress and ischemic injury, and by engaging pro-survival cascades. During its cardioprotective action, CgA does not impair the antitumor activity of anthracyclines (i.e. doxorubicin) in tumor-bearing mice of melanoma, fibrosarcoma, lymphoma and lung cancer. On the other hand, the invention indicates that administration of doxorubicin to rats and of a chemoterapic regime also including doxorubicin to lymphoma and breast cancer patients can reduce the endogenous CgA in the blood, i.e. of a potential protective factor. These findings suggest the impact of CgA as potential biomarker and cardioprotective co-adjunct during anthracyclines regimens.

Possible Applications

• Administration of CgA, in particular to patients with low levels of endogenous CgA, might prevent anthracyclines-induced adverse events without impairing their antitumor effects;
• CgA might represent a diagnostic/prognostic biomarker for the anthracyclines-induced cardiotoxicity in cancer patient.

Advantages

• CgA exerts cardioprotection against doxorubicin-induced cardiotoxicity at physiological doses;
• CgA resembles a physiological protein;
• CgA does not impair the anticancer activity of doxorubicin;
• CgA might likely apply to patients with non-neuroendocrine tumors under doxorubicin treatment.