A new type of gene therapy delivered using a virus that could protect healthy tissues from the harmful side-effects of radiotherapy after cancer (lat. Prostate Carcinoma) treatment has been discovered by the researchers at The Institute of Cancer Research. 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 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 team at the 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 the 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 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 tumour cells were not protected by the treatment, and stayed vulnerable to radiotherapy.
Tumours in rats that had been treated with the gene therapy responded better to radiotherapy - with tumour growth stopped for 40 days in four out of five animals. By protecting the healthy tissues around tumours, the gene therapy increased the effectiveness of radiotherapy - although more research is needed to find out how and why this happens. This study has found a clever new way to deliver gene therapy using a virus so that healthy tissue is protected from radiotherapy side-effects while tumour cells remain vulnerable to the treatment.