BREACHING CANCER’S DEFENCES

Researchers have shown that an experimental drug combination could help break a tumour’s resistance to immunotherapy

THE IMMUNOTHERAPY DRUG pembrolizumab has been successful in treating a range of solid tumours. But cancers can develop resistance to the drug, and some patients who initially benefit from it will eventually see their disease worsen.

Now, in a study supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre (BRC) at The Royal Marsden and The Institute of Cancer Research, London (ICR), researchers have shown that combining pembrolizumab with the experimental drug guadecitabine may reverse a cancer’s resistance to immunotherapy – making it sensitive to treatment again. Guadecitabine is a DNA hypomethylating agent, which means it works by removing methyl groups from DNA. Methylation of cancer DNA is thought to play a role in cancer’s ability to suppress the immune system and therefore evade the action of immune checkpoint inhibitor drugs such as pembrolizumab.

Researchers at The Royal Marsden and the ICR found that 37 per cent of patients who received the drugs in tandem had their cancer kept in check for 24 weeks or more. The combination treatment could be a new option for patients with lung cancer or other tumours whose disease has progressed and become resistant to immunotherapy.

“Immunotherapy has shown amazing promise over the past decade, but it doesn’t work well in all cancers, and cancers can often become resistant,” says study lead

Dr Anna Minchom, a NIHR BRC Clinical Scientist in the Oak Drug Development Unit and a Consultant Medical Oncologist at The Royal Marsden, who is funded by The Royal Marsden Cancer Charity.

“It was interesting to explore the guadecitabine–pembrolizumab combination in this study, as it could have the ability to reverse a resistance to immunotherapy and potentially benefit a large number of patients.”

Professor Johann de Bono, Director of the Oak Drug Development Unit at The Royal Marsden and the ICR and the study’s Chief Investigator, adds:

“If these effects are confirmed in other patient groups and future studies, in the long term, guadecitabine and pembrolizumab could help to tackle some of the resistance to immunotherapy we see in too many types of cancer.” RM

What is the Biomedical Research Centre?

The National Institute for Health and Care Research-funded Biomedical Research Centre for cancer is a partnership between The Royal Marsden and The Institute of Cancer Research, London. It supports the rapid translation of leading-edge cancer research from the laboratory into a clinical setting. Find out more at cancerbrc.org