New preclinical study from the Institute of Cancer Research, London, reveals potential for CXCL12-targeted therapy to reduce radiotherapy complications
A groundbreaking new study from researchers at The Institute of Cancer Research (ICR), London, suggests that silencing a key gene involved in tissue scarring—CXCL12—could significantly reduce the formation of fibrotic tissue following radiotherapy. The discovery could ultimately improve treatment outcomes and quality of life for breast cancer patients, especially those undergoing reconstructive surgery after treatment.
Radiation-induced fibrosis (RIF), a common and often debilitating side effect of radiotherapy, results from tissue damage that leads to inflammation and excessive scar formation. For breast cancer survivors, RIF can lead to chronic pain, reduced mobility, and cosmetic deformities. It also complicates reconstructive surgery and delays physical and emotional recovery.
In a preclinical study using a rat model, researchers explored whether gene therapy targeting CXCL12 could prevent fibrosis and improve therapeutic responses. The gene CXCL12 has been previously implicated in other fibrotic conditions, such as cirrhosis and pulmonary fibrosis, but its role in RIF had not been examined in detail until now.
Led by Dr Aadil Khan, Consultant Plastic Surgeon at The Royal Marsden and honorary appointee at the ICR, and US-based breast reconstruction surgeon Dr James T Paget, the team used lentiviral vectors to either silence or overexpress CXCL12 in skin tissue prior to radiation exposure. They found that silencing the gene not only preserved normal tissue architecture but also thinned the fibrotic capsule that typically forms around tumours post-radiotherapy—thereby enhancing immune cell infiltration and tumour responsiveness to treatment.
“Our findings suggest that CXCL12 is a key driver of the immune response to radiotherapy, and silencing it can reduce fibrosis while improving tumour access for immune cells,” said Dr Khan. “This could make radiotherapy more effective, especially for resistant tumours surrounded by dense scar tissue.”
The study, published in Molecular Cancer Therapeutics, was primarily funded by the Wellcome Trust, with additional support from the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR.
While the current research relied on gene therapy—still largely experimental in human applications—the authors suggest that pharmacological inhibitors targeting the CXCL12 pathway could offer a more clinically viable approach in the future.
“Our study introduces a potential ‘win-win’ therapeutic strategy: one that could both minimise the damaging side effects of radiotherapy and enhance its effectiveness,” Dr Khan added.
Professor Kevin Harrington, co-author and Professor of Biological Cancer Therapies at the ICR, emphasised the broader impact of the findings: “Scar tissue following radiotherapy is a major clinical challenge. By targeting CXCL12, we may be able to reduce these complications and improve quality of life for many patients.”
Further research will be needed to determine how this approach might also affect the tumour’s permeability to systemic treatments such as chemotherapy and immunotherapy—raising hope for multi-pronged cancer therapies with fewer long-term consequences for survivors.
