A new type of gene therapy delivered using a virus could protect healthy tissues from the harmful side effects of radiotherapy after cancer treatment, a new study reports. In the future, the treatment could be used to improve outcomes for breast reconstruction surgery in women with breast cancer by protecting patients from scarring, shrinkage of the skin and damage to the underlying tissues.
Scientists at The Institute of Cancer Research, London, found they could prevent tissue damage in rats treated with radiotherapy by reprogramming healthy cells to protect themselves. Modern radiotherapy is increasingly precise and targeted, but even so it can still cause a variety of side effects to tissues, including skin, fat and blood vessels, months or years after treatment.
The protection given by the new gene therapy could prevent radiotherapy side effects in women who have had breast reconstruction surgery and spare women a second operation to repair the damage caused by delayed side effects.
The study was published in the journal Science Translational Medicine.
The team at The Institute of Cancer Research (ICR), in collaboration with plastic surgeons at The Royal Marsden NHS Foundation Trust, injected rats with a modified and harmless version of a type of virus called a lentivirus. The virus was used to deliver extra copies of a gene called SOD2, which plays a role in limiting the stress response to the harmful particles released by radiotherapy. The team combined this with a second virally delivered treatment to block activity of a different gene involved in the scarring response to radiotherapy, called CTGF.
Six months after radiotherapy, transplanted tissues in rats that had been treated with a combination of SOD2 and CTGF gene therapy had shrunk by just 15 percent, compared with 70 percent in those that had not received either treatment.
The viral therapy was injected into blood vessels in tissue before it was transplanted to ensure that the protective effect was isolated only to healthy tissue away from the cancer - and to model the situation in which the gene therapy would be delivered in the clinic.
The amount of SOD2 and CTGF did not increase in the area outside the transplanted tissue, meaning that tumor cells were not protected by the treatment and stayed vulnerable to radiotherapy.
Tumors in rats that had been treated with the gene therapy responded better to radiotherapy, with tumor growth stopped for 40 days in four out of five animals.
The findings suggest that by protecting the healthy tissues around tumors, the gene therapy increased the effectiveness of radiotherapy, although more research is needed to find out how and why this happens.
The two gene therapies targeting the CTGF gene and the SOD2 gene, respectively, seemed to counteract radiotherapy damage in healthy tissue through different mechanisms, suggesting that a combination of the two therapies would be most beneficial.
The new study opens up the possibility of offering women with breast cancer earlier reconstruction surgery, using tissues that are protected from radiotherapy side effects. The next step will be to test out the new treatment in clinical trials.
Science Translational Medicine, January 24, 2018
The Institute of Cancer Research, London (http://www.icr.ac.uk)