Research Discovery: How Topobexin Prevents Heart Damage From Chemotherapy

Sep 10 2:02pm | Jasmine Souers | @jasminesouers

Researchers discovered a new way to block a heart-damaging protein called TOP2B using a specially designed molecule named topobexin, which fits into a unique pocket like a key in a lock. This breakthrough allows topobexin to protect the heart during chemotherapy without interfering with cancer treatment, identifying a brand-new way of reducing toxicity of cancer therapies and offering a safer option for patients.

What It Is

This study introduces topobexin, a newly developed drug designed to protect the heart from damage caused by certain chemotherapy treatments, specifically anthracyclines like doxorubicin. These drugs are powerful cancer fighters but can cause serious heart problems over time.

How It Works

Topobexin works by selectively blocking a protein called Topoisomerase II beta (TOP2B), which is found in heart cells and is linked to chemotherapy-induced heart damage. Unlike older drugs like dexrazoxane, which block both TOP2A (important for killing cancer cells) and TOP2B, topobexin is precise—it targets only TOP2B. This means it protects the heart without interfering with the cancer-fighting effects of chemotherapy.

Key Findings

Topobexin binds to a newly discovered pocket in the TOP2B protein, acting like a “lock” that prevents harmful changes.

In lab tests and animal models, topobexin prevented heart cell damage, reduced signs of stress and inflammation, and preserved heart function.

It was more effective and safer than dexrazoxane, requiring lower doses and showing no toxicity.

Importantly, it did not reduce the effectiveness of chemotherapy in killing cancer cells.

Community Impact

This breakthrough could significantly improve the quality of life for cancer survivors, especially children, by reducing long-term heart damage from chemotherapy. It also opens the door to safer cancer treatments and better tools for studying heart health and gene regulation.

Study: "Topobexin targets the Topoisomerase II ATPase domain for beta isoform-selective inhibition and anthracycline cardioprotection"

Researcher: M. Schellenberg, Ph.D.

Learn more: https://doi.org/10.1038/s41467-025-60167-9