Cancer Research UK-funded scientists at the University of Cambridge, in collaboration with the Spanish National Cancer Research Centre (CNIO) and Cambridge-based startup Tailor Bio, have created a test which can successfully predict whether cancer will resist common forms of chemotherapy treatment.
It works by looking at changes to the order, structure and number of copies of DNA within the cancer - known as chromosomal instability (CIN) signatures. These signatures are found by reading the full DNA sequence of the tumour and looking for patterns in how the chromosomes are disrupted when compared to normal cells
The test can then accurately predict resistance to treatment of three common types of chemotherapy – platinum-based, anthracycline and taxane chemotherapy. Cancer Research UK and NHS England analysis shows that tens of thousands of people are treated with platinum- and taxane-based chemotherapies every year in England*.
Chemotherapy is an effective form of cancer treatment but can be toxic to healthy cells as well as cancer cells, resulting in unpleasant side-effects. In the future, scientists hope that this test could be used at diagnosis to predict how likely each type of chemotherapy will work against different cancers. This would allow them to offer tailored treatment, by avoiding giving patients chemotherapies which won't work for them.
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, Professor James Brenton, said:
"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 treatment – 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."
Dr Geoff Macintyre, lead author, Group Leader at the Spanish National Cancer Research Centre (CNIO) and CSO at Tailor Bio says:
"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."
Dr Ania Piskorz, co-lead author and Head of Genomics at Cancer Research UK Cambridge Institute, added:
"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."
The test was piloted using data from 840 patients with different types of cancer. It was used to classify patients as either "chemotherapy resistant" or "chemotherapy sensitive", after which they were virtually assigned to a different type of chemotherapy treatment to find out how long it took for the treatment to stop working. This approach emulated a randomised controlled trial by allowing the scientists to predict patient responses to chemotherapy, without altering the treatment the patients received.
Fiona Barvé is a retired secondary school biology teacher from Cambridge, who was diagnosed with ovarian cancer in 2017 and treated at Addenbrooke's Hospital. She received the "all clear" in 2019 but her cancer returned in April 2022. She received further surgery and chemotherapy and is now on olaparib, a drug developed by Cancer Research UK-funded scientists in Cambridge to prevent breast and ovarian cancers from coming back.
Since 2019, Fiona has served on Cambridge's Women+s Cancers Patient and Public Involvement Group. The Group raises awareness of women's cancers and helps cancer researchers at the Cancer Research UK Cambridge Centre's Women+s Cancers Programme to plan and design research projects like this one.
Welcoming the findings of this research, 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."
The trial found that patients who had predicted resistance to taxane chemotherapy had a higher treatment failure rate for ovarian metastatic breast and metastatic prostate cancer. Patients who had predicted resistance to anthracycline chemotherapy had a higher treatment failure rate for ovarian and metastatic breast cancer. Patients who had predicted resistance to platinum chemotherapy had a higher treatment failure rate for ovarian cancer.
The technology behind the test was developed at the University of Cambridge with funding from Cancer Research UK. Cancer Research Horizons, the charity's innovation arm, then licensed the technology to Tailor Bio, a company which creates targeted treatments for cancers with CIN signatures.
Working with the CNIO in Madrid and Tailor Bio, the scientists at the Cancer Research UK Cambridge Institute will carry out further analysis of the test and will be applying to regulators for use in clinic. The scientists are also developing further tests for other targeted cancer drugs to find out how widely the technology could be used across different cancer types.
Executive Director of Research and Innovation at Cancer Research UK and CEO of Cancer Research Horizons, Dr Iain Foulkes, said:
"The days of chemotherapy being offered as a 'one-size-fits-all' treatment are ending. Thanks to this research, and others like it, we are moving towards a future where personalised cancer treatment is an option for many patients. Only by delivering more optimised, successful treatment will more people live longer, better lives, free from the fear of cancer."
This personalised treatment approach underpins the vision of Cambridge Cancer Research Hospital, a specialist cancer research hospital due to be built on Europe's leading life sciences campus, the Cambridge Biomedical Campus. It will bring clinical expertise from Addenbrooke's Hospital with world-class scientists from the University of Cambridge, Cancer Research UK Cambridge Centre, and industry partners together in one location to create new diagnostics and treatments to detect the earliest signs of cancer and deliver personalised, precision medicine.
