A novel CRISPR-based genetic screening method has enabled Stanford Medicine researchers to pinpoint a key gene responsible for heart cell damage caused by the chemotherapy drug doxorubicin. The discovery may pave the way for new therapies to protect the heart during cancer treatment.
Doxorubicin, while effective at killing cancer cells, is known to cause cardiotoxicity, leading to arrhythmias, impaired organization, and cell death in heart cells. High doses or prolonged use can result in heart failure, limiting the drug's application despite its efficacy against various cancers. According to Joseph Wu, MD, PhD, a professor of cardiovascular medicine and director of the Stanford Cardiovascular Institute, the goal has always been to find a way to prevent this toxicity.
CRISPR Screen Uncovers Key Gene
To identify the genes involved in doxorubicin-induced heart damage, Wu and Stanley Qi, PhD, an associate professor in bioengineering, developed a genetic screening tool using CRISPR technology. This screen targeted 2,300 genes already known to be targeted by existing drugs, ultimately highlighting one gene as a critical mediator of doxorubicin's harmful effects.
"This CRISPR screen is a valid tool for drug discovery," Wu stated. "That, to me, is the key take-home message of the study."
The study, published in Cell Stem Cell, details how the CRISPR screen allowed researchers to sift through a large number of genes to find the critical factor in doxorubicin-induced cardiotoxicity.
Implications for Cardioprotection
The identification of this key gene opens avenues for developing targeted therapies to protect heart cells during chemotherapy. The researchers also identified a drug that could potentially safeguard heart cells from doxorubicin's damaging effects. Further research is needed to validate these findings and translate them into clinical applications, potentially improving the safety and efficacy of cancer treatment regimens.
