New Hope for Preventing Doxorubicin’s Heartbreaking Side Effect
Doxorubicin is a powerful weapon in the fight against cancer, effectively eliminating cancerous cells. But its potential benefits come with a devastating side effect: it can damage the heart. This damage can manifest as irregular heartbeats, disorganization within heart tissue, and even cell death. If used in high doses or for extended periods, doxorubicin can lead to heart failure, significantly limiting its use despite its effectiveness against cancer.
“We’ve always wanted to find a way to stave off this toxicity,” said Joseph Wu, MD, PhD, a professor of cardiovascular medicine and the director of the Stanford Cardiovascular Institute.
Now, researchers at Stanford Medicine may have made a crucial breakthrough in understanding how doxorubicin harms the heart, potentially paving the way for safely using this invaluable chemotherapy drug. They’ve developed a groundbreaking genetic screening tool, harnessing the power of CRISPR, a gene-editing technology, to identify the genes involved in doxorubicin-induced heart damage. This innovative tool has pinpointed a specific gene that appears to be a key player in the damage inflicted by the drug.
“This CRISPR screen is a valid tool for drug discovery,” said Wu, who is also the Simon H. Stertzer, MD, Professor. “That, to me, is the key take-home message of the study.”
This research, published in Cell Stem Cell on November 7, was led by Chun Liu, PhD, an assistant professor at the Medical College of Wisconsin and a former Stanford Medicine postdoctoral researcher, and Mengcheng Shen, PhD, a researcher and instructor at the institute. Wu and Stanley Qi, PhD, an associate professor in bioengineering and a scholar at Sarafan ChEM-H, share senior authorship.
Creating this new genetic screening tool was a major achievement in itself. The researchers knew doxorubicin caused heart damage, but they didn’t know which genes were involved. They decided to focus on a manageable number of genes, narrowing their search to 2,300 genes already targeted by existing drugs.
By analyzing the effects of manipulating these genes in the presence of doxorubicin, the researchers were able to identify a crucial target – a gene that appears to be directly involved in the heart damage caused by the drug.
This discovery opens up exciting new possibilities for developing therapies that can protect the heart from doxorubicin’s toxic effects. By targeting this identified gene, researchers may be able to develop drugs that prevent or reduce heart damage without compromising the drug’s ability to kill cancer cells. This could lead to safer and more effective cancer treatments,
"We are very excited about the potential of this discovery," said Wu. “It represents a major step forward in our understanding of doxorubicin toxicity and could lead to the development of life-saving drugs that will enable us to use this powerful chemotherapy agent more safely and effectively."
What are the harmful side effects of Doxorubicin on the heart?
## Searching for a Solution: A New Hope in the Fight Against Doxorubicin’s Cardiac Side Effects
**Host:** Joining us today is Dr. Joseph Wu, MD, PhD, Professor of Cardiovascular Medicine and Director of the Stanford Cardiovascular Institute, who’s leading groundbreaking research into minimizing the heart-damaging effects of the chemotherapy drug, doxorubicin.
Welcome to the show, Dr. Wu.
**Dr. Wu:** Thank you for having me.
**Host:** Doxorubicin is a vital weapon in our fight against cancer, but its potential for cardiac damage is a serious concern. Can you tell us more about this side effect and why it’s so challenging?
**Dr. Wu:** Doxorubicin is incredibly effective at killing cancer cells, but unfortunately, it can also harm healthy heart muscle cells. This damage can lead to irregular heartbeats, disorganized heart tissue, and even cell death.
If patients receive high doses or undergo prolonged treatment, it can ultimately lead to heart failure. This limits the amount of doxorubicin we can use to treat cancer effectively, putting patients at risk. [[1](https://pmc.ncbi.nlm.nih.gov/articles/PMC8493405/)]
**Host:** That’s incredibly alarming. What steps is your team taking to address this problem?
**Dr. Wu:** We at Stanford Medicine are focused on understanding the exact mechanisms by which doxorubicin harms the heart. We’ve developed a powerful new tool using CRISPR gene-editing technology. This CRISPR screen allows us to systematically investigate thousands of genes simultaneously to pinpoint those involved in doxorubicin-induced heart damage.
**Host:** And what have you discovered so far?
**Dr. Wu:** Our research has identified a specific gene that appears to be a critical player in the damage caused by doxorubicin. This discovery is a major step forward and opens avenues for developing new therapies that could protect the heart from this damaging side effect.
**Host:** So, this CRISPR-based research could potentially lead to safer ways to use doxorubicin, allowing us to harness its anti-cancer power without putting the heart at risk?
**Dr. Wu:** That’s exactly our hope. This CRISPR screen is proving to be a valuable tool not just for understanding doxorubicin’s side effects, but also for broader drug discovery efforts.
**Host:** This is truly exciting news, Dr. Wu. Thank you for shedding light on this crucial research and giving us hope for the future of cancer treatment.
**Dr. Wu:** Thank you for having me.
