CgA AS NOVEL BIOMARKER AND PROTECTOR IN THE CARDIOTOXICITY
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.
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.
- 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.
- 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.