Radiation therapy is commonly used to prevent recurrence of breast cancer. Precisely delivered, modern radiation therapy is an effective cancer killer, greatly reducing the risk of recurrence. But it also has a downside: it targets tissue indiscriminately, damaging healthy tissue along with diseased.
Radiation can be problematic for women who have breast reconstruction after mastectomy, particularly reconstruction with breast implants. Because while radiation successfully disrupts the DNA of cancer cells so that they’re unable to reproduce, it also permanently changes the molecular structure of surrounding healthy tissue, reducing blood flow and elasticity in the skin. Radiated tissue tends to tighten and shrink, compromising the shape, size and position of a reconstructed breast. It’s a particularly poor combination with breast implants.
Gene therapy might protect healthy tissues from the harmful side-effects of radiotherapy and minimize the detrimental effects of radiation.
Human gene therapy modifies certain cells with new genetic material for therapeutic benefit. Sounds very space-agey (and it is), but some forms of gene therapy are already FDA-approved and used in vaccines for certain cancers, immunotherapies, and other treatments. The potential of gene therapy is enormous. One day, it may be possible to mitigate the high risk for cancer and disease of someone who has a defective or missing gene—individuals who have a mutation in either BRCA1 or BRCA2 or other cancer-causing gene might have an injection of correcting genetic material to restore function of the defective gene. Increasingly, gene therapy for diseases that have no other cure is showing promise in clinical trials—hundreds of such trials are already underway. One particular trial suggests that gene therapy may dramatically reduce the damaging effects of radiation on healthy tissue.
Delivering gene therapy with a virus
At The Institute of Cancer Research in London, a harmless, modified virus was used to deliver two types of gene therapy to rats that had previously been injected with tumor cells: extra copies of the SOD2 gene, to limit the body’s stress response to radiation’s harmful particles, and a treatment to block the CTGF gene involved in scarring from radiation therapy. The virus/gene therapy was injected into the animal’s blood vessels in tissue that was then transplanted (transplanting the treated tissue ensured that the protective effect was isolated only to healthy and not cancerous tissue, and to model the situation in which the gene therapy would be delivered in the clinic). The rats were then given radiation therapy.
After 6 months, the genetically treated tissue had shrunk by only 15%, compared to 70% in rats that had not received gene therapy. Delivering the combination of gene therapies appeared to counteract radiation damage to healthy tissue, while also improving the effectiveness of the radiation (more research is needed to find out how and why this happened).
Kevin Harrington, Professor of Biological Cancer Therapies at the ICR, said: “Some women who need radiotherapy after a mastectomy have to wait up to six months after the end of their treatment before they can have breast reconstruction surgery, to allow time for side-effects to show themselves…we hope this new viral gene therapy could protect healthy tissue transplanted during cancer surgery, bringing forward the subsequent operation to reconstruct the breast.”
It’s not as easy as it sounds, and researchers face a variety of challenges, including methods of delivery, how to precisely target the right cells, and ensuring that the recipient’s body can control the new genes in the desired way before gene therapy becomes a reliable method of treating diseases. Gene therapy is a long way from practical clinical use, but this study offers new hope that radiation therapy will not compromise the quality of a woman’s post-mastectomy body, and specifically, her breast reconstruction.
The next step will be to test the new treatment in clinical trials.
Khan AA, Paget JT, McLaughlin M, et al. “Genetically modified lentiviruses that preserve microvascular function protect against late radiation damage in normal tissues.” Science Translational Medicine. 2018; 10(425): eaar2041.