Mechanisms and management of doxorubicin cardiotoxicity

Area of Science:

• Cardiology
• Oncology
• Pharmacology

Background:

• Doxorubicin (DOX) is a widely used chemotherapy agent effective against various cancers.
• However, DOX exhibits cumulative dose-dependent cardiotoxicity, leading to doxorubicin-induced cardiomyopathy (DIC).
• The precise mechanisms underlying DOX cardiotoxicity are complex and multifactorial, involving oxidative stress, iron metabolism, and emerging pathways.

Purpose of the Study:

• To review the multifaceted mechanisms of doxorubicin cardiotoxicity.
• To discuss current and potential therapeutic strategies for preventing or treating DOX-induced cardiac damage.
• To highlight novel approaches for enhancing cardiomyocyte resistance to DOX toxicity.

Main Methods:

• Literature review of studies investigating doxorubicin cardiotoxicity mechanisms.
• Analysis of proposed and experimental preventive and therapeutic interventions.
• Synthesis of information on emerging strategies targeting specific molecular pathways.

Main Results:

• Doxorubicin toxicity involves iron/redox reactions, abnormal protein processing, innate immune activation, and impaired neuregulin-1 (NRG1)/ErbB(HER) signaling.
• Other mechanisms include reduced progenitor cell renewal, impaired cardiac repair, and decreased vasculogenesis.
• No clinically proven treatment currently exists for doxorubicin cardiomyopathy.

Conclusions:

• Understanding the diverse mechanisms of DOX cardiotoxicity is crucial for developing effective interventions.
• Existing strategies like dexrazoxane, ACE inhibitors, and beta-blockers show promise but require further validation.
• Novel approaches targeting specific pathways, such as anti-miR-146 or recombinant NRG1, offer future therapeutic potential for mitigating DOX cardiotoxicity.