Scientists develop test to predict resistance to chemotherapy treatment

Cancer Research UK-funded scientists at the University of Cambridge, in partnership with the Spanish National Cancer Research Centre (CNIO) and the Cambridge-based start-up Tailor Bio, have developed a test that can accurately predict whether a cancer is likely to resist common forms of chemotherapy.

The test examines chromosomal instability signatures – changes to the order, structure and number of DNA copies within the tumour. These are detected by sequencing the full DNA of the tumour and identifying patterns of chromosomal disruption compared to normal cells.

The test can predict resistance to three widely used types of chemotherapy: platinum-based, anthracycline and taxane treatments. According to Cancer Research UK and NHS England, tens of thousands of patients in England receive platinum- and taxane-based chemotherapy each year.

While chemotherapy remains a cornerstone of cancer treatment, its toxicity to healthy cells often results in severe side effects. In future, this test could be used at diagnosis to indicate how likely a tumour is to respond to specific chemotherapies, allowing clinicians to tailor treatment and avoid using drugs that are unlikely to be effective.

“Chemotherapy is a mainstay of cancer treatment and saves many lives. Yet in many cases, it has been administered the same way for over 40 years. Sadly, there are too many cases where cancer is resistant to chemotherapy – meaning unpleasant side effects for the patient with limited benefit to them.

“With genomic sequencing now more widely available, we can make some of the most well-established chemotherapies work better. By understanding who is most likely to respond to it, chemotherapy could become a more tailored treatment across different types of cancer,” said Professor James Brenton, Professor of Ovarian Cancer Medicine at the Cancer Research UK Cambridge Institute and Honorary Consultant in Medical Oncology at Cambridge University Hospitals NHS Foundation Trust.

Dr Geoff Macintyre, lead author, Group Leader at CNIO and Chief Scientific Officer at Tailor Bio, added: “Our technology makes sense of the genomic chaos seen in many tumours treated with chemotherapy. It links patterns of DNA mutation to the mechanisms that caused the damage.

“This provides a read-out of the defective biology in the tumour which we can use to predict resistance to the mechanism of action of common chemotherapies,” he added.

And Dr Ania Piskorz, co-lead author and Head of Genomics at the Cancer Research UK Cambridge Institute, also commented: “It was important to us to create a test that could be easily adopted in clinic, using material we already collect during diagnosis and well-established genomic sequencing methods.

The test is based on the full DNA sequence that we get from these methods, and we can adapt it to work alongside other genomic sequencing methods that are commonly used to personalise treatment for cancer,” she said.

The test was trialled using data from 840 patients with various cancer types. Patients were categorised as either ‘chemotherapy resistant’ or ‘chemotherapy sensitive’, and then virtually reassigned to different chemotherapy regimens. The team analysed how long it took for treatments to fail, mimicking the design of a randomised controlled trial without altering the care received by the patients.

One of the patients supporting the research is Fiona Barvé, a retired secondary school biology teacher from Cambridge who was first diagnosed with ovarian cancer in 2017 and treated at Addenbrooke’s Hospital. After being given the ‘all clear’ in 2019, her cancer returned in April 2022. She underwent further surgery and chemotherapy and is now on olaparib, a drug developed by Cancer Research UK-funded scientists in Cambridge to prevent recurrence in breast and ovarian cancers.

Since 2019, Fiona has been an active member of the Women+s Cancers Patient and Public Involvement Group in Cambridge, which supports awareness-raising and research design.

Welcoming the new findings, Fiona said: “Undergoing chemotherapy is both a physical and mental process. Fatigue as well as physical long-term side effects are present for months after the treatment.

“Everybody who’s joined the patient group wants to help with the research and wants to help future patients, because ultimately most of us will not be around to actually get any benefit from it. I believe the personalised aspect of my treatment was very important. It allows you to know that you have a higher probability of succeeding in your trials.

“Using a personalised method to identify the correct chemotherapy regime for each individual patient can only be positive for all patients. It also helps to remove unnecessary stress and unnecessary drugs being used,” she said.

The trial revealed that patients predicted to be resistant to taxane chemotherapy had a higher treatment failure rate in ovarian, metastatic breast and metastatic prostate cancers. Resistance to anthracycline chemotherapy was associated with increased failure in ovarian and metastatic breast cancers. For platinum-based chemotherapy, predicted resistance correlated with worse outcomes in ovarian cancer.

The test was developed at the University of Cambridge with support from Cancer Research UK. Cancer Research Horizons, the charity’s innovation division, licensed the technology to Tailor Bio, a start-up focused on developing targeted treatments for cancers exhibiting CIN signatures.

In collaboration with CNIO and Tailor Bio, scientists at the Cancer Research UK Cambridge Institute will now carry out further validation studies and seek regulatory approval for clinical use. They are also working on additional tests for other targeted cancer therapies to explore the wider applicability of the approach.

For further reading please visit: 10.1038/s41588-025-02233-y