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Problem Addressed

Anticancer treatment cardiotoxicity limits the efficacy of cancer therapies. A common therapeutic of the anthracycline family is doxorubicin (DOX). Prior attempts to prevent DOX-induced cardiotoxicity include total dose limitation, liposomal delivery, and pharmacologic prevention; however, these tactics are confined by various factors. They can weaken the antitumor potency of treatment, are not easily controlled or thoroughly understood, and are not validated in randomized clinical trials. In another method, such as DOX-encapsulating, polymeric nanoparticles, difficulties in optimization of drug loading and tissue targeting for local delivery have arisen. Furthermore, monomeric ligands used to inhibit HER-initiated intracellular signaling pathways — including small molecule kinase inhibitors, ligand binding blocking antibodies, and sterically-oriented dimerization inhibiting antibodies — are not as cardioprotective as ligand dimers. The invention provides bivalent ligand compositions and controlled methods for reducing, preventing, and reversing cardiotoxicity effects while improving the efficacy of the therapeutic agents. It has also been found to treat heart dysfunction and reverse the effects of myocardial infarctions.