Radiation therapy is highly effective at killing cancer cells, but it often harms healthy skin around the treatment area, a common side effect experienced by up to 95% of cancer patients undergoing treatment. In worst-case scenarios, it can result in delayed or halted treatment.

 

Researchers at Houston Methodist Research Institute have now discovered a promising new approach that can protect patients from radiation-induced skin damage during cancer treatment.

 

The researchers tested a new mRNA-based therapy that instructs skin cells to produce telomerase reverse transcriptase (TERT), a protein known for its role in cell health. Human skin cells and tissue samples were treated with TERT mRNA prior to radiation exposure, resulting in reduced DNA damage. The study, published in Molecular Therapy, was led by John Cooke, M.D., Ph.D., chair of the Department of Cardiovascular Sciences at the Houston Methodist Research Institute.

 

“Telomerase has this very interesting effect to protect against genomic DNA damage,” Cooke said. “That is surprising because it is usually believed that it only works at the ends of chromosomes, but we’re finding it helps keep all of our DNA safe.  We could reverse clinically relevant doses of radiation-induced DNA damage with telomerase. This is exciting because it could potentially be a therapy to help people who undergo radiotherapy.”

 

Radiation-induced skin injury is one of the most common and painful side effects of cancer treatment. Radiation injurycauses microvascular damage andcan lead to redness, peeling, ulcers, infections and long-term scarring, sometimes forcing doctors to delay or stop cancer treatment. Radiation-induced damage on the skin can break DNA inside skin cells, disrupt mitochondria (the cell’s energy centers) and trigger cell death.

 

Currently, no FDA-approved therapy exists to prevent or treat radiation-induced skin damage.

 

“Our findings suggest that TERT mRNA therapy could offer a safe and effective way to protect skin, improve patient comfort and allow uninterrupted cancer care,” said first author Shuang Li, a research fellow in the Department of Cardiovascular Sciences at Houston Methodist DeBakey Heart and Vascular Institute. “This breakthrough could lead to new therapies that prevent radiation burns and long-term scarring, improving quality of life for millions of cancer patients.”

 

Other collaborators in the study include David Chang, Karem Court, Thi Kim Cuc Nguyen, Vrutant Shah, Elisa Morales, Jack Carrier, Anjana Tiwari, Kristopher Brannan, Aldona Spiegel, Maham Rahimi, Jeffrey Friedman, Elizabeth Olmstead-Davis, Biana Godin and Anahita Mojiri from Houston Methodist and Andrew Ludlow from the University of Michigan.

 

The study is supported by grants from the National Heart, Lung and Blood Institute (1R01HL148338, 1R01HL133254), the Cancer Prevention Research Institute of Texas (RP200619), George and Angelina Kostas Research Center for Cardiovascular Nanomedicine and the Congressionally Directed Medical Research Programs/Department of War Medical Burn Program grant (MB230026).