A new DNA test could one day help doctors find which chemotherapy drugs are most likely to work for their patients, according to research we helped fund. 

It works by scanning cancer cells for signs they are sensitive or resistant to three of the most common types of chemotherapy treatments: platinum based, anthracycline and taxane chemotherapy.  

With this insight, doctors should be able to give people with cancer the most suitable chemotherapy from the very start of treatment, avoiding side effects from drugs that aren’t likely to work.

As well as helping personalise chemotherapy, the test could also show when people need other types of cancer treatment or should be invited to join clinical trials. 

Researchers at our Cambridge Institute designed the test to work using current DNA reading (or genome sequencing) technology, which should make it easier to introduce to standard cancer care. They’re now working with the Spanish National Cancer Research Centre (CNIO) and Cambridge company Tailor Bio to validate the test for the next round of clinical trials.

James Brenton, Professor of Ovarian Cancer Medicine at our Cancer Research UK Cambridge Institute, 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.” 

Using tumour biology to detect resistance

Chemotherapy is the most common treatment for cancer, and tens of thousands of patients are treated with taxane and platinum-based chemotherapy drugs each year in the UK. However, some cancers have adaptations that help them resist these drugs, and they can also harm healthy cells, leading to difficult side effects like brain fog, hair loss and numbness in the hands and feet.

Until now, it hasn’t been possible to predict which patients are less likely to benefit from chemotherapy, meaning some people experience those side effects from drugs that aren’t the best options for treating their cancer. 

To try and address that problem, researchers at our Cambridge Institute began investigating cancer DNA for patterns that appear in tumours that are harder to treat with chemotherapy. 

That work led to the new test, which looks for specific patterns of changes to the order, structure and number of copies of DNA in the cells of a tumour. These ‘chromosomal instability’ (CIN) signatures can be picked out from the results of standard genomic sequencing, giving doctors a completely new way of understanding how cancers may respond to treatment.

“Our technology makes sense of the genomic chaos seen in many tumours treated with chemotherapy,” said Dr Geoff Macintyre, who works at CNIO and Taylor Bio. “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.” 

The research team trialled the test by applying it to preexisting data from 840 patients with different types of cancer.

First, the team analysed genomic data to find CIN signatures and divide the participants of their virtual clinical trial into ‘chemotherapy resistant’ and ‘chemotherapy sensitive’ groups for each type of chemotherapy. They then tracked how well the treatments worked for people in each group.

This approach made it possible to predict patient responses to different chemotherapies without impacting the treatment they were already receiving. Now, it has shown that certain CIN signatures can be used to predict when chemotherapies are least likely to work.

The researchers are now applying to regulators to plan out what further trials will be needed to make sure the test is suitable for standard NHS practice. After that, it could help doctors across the UK use some of their main cancer treatments more precisely and effectively. 

Dr Iain Foulkes, our executive director of research and innovation, said: “The days of chemotherapy being offered as a ‘one-size-fits-all’ treatment are ending. Thanks to this research, and other research like it, we’re moving towards a future where personalised cancer treatment is a daily reality for patients.” 

Entering an era of precision chemotherapy

Among those who welcome the findings of this trial is cancer survivor and patient advocate Fiona Barvé.

Fiona, who was diagnosed with ovarian cancer in 2017 and has first-hand experience of being treated with chemotherapy, is a member of the Cambridge’s Women+s Cancers Patient Involvement Group, which works to raise awareness of women’s cancers.

Although her first treatment was successful, Fiona’s cancer returned in April 2022 and she underwent further surgery and chemotherapy. She’s now receiving a targeted (or personalised) drug called olaparib, which helps to prevent her cancer returning by exploiting a weakness doctors found in her cancer cells.  

Reflecting on her treatment, 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.”