Scientists have developed a test which successfully predicts whether cancer will resist common forms of chemotherapy treatment
Chemotherapy has been the gold standard treatment for cancer for decades and works by destroying tumour cells. However, it is not always effective. To address this challenge, a team of researchers from Cancer Research UK, in collaboration with the Spanish National Cancer Research Centre (CNIO) and Cambridge-based startup Tailor Bio, have created a test that can predict chemotherapy resistance in patients. This collaborative effort underscores the shared purpose and unity in the fight against cancer.
“Chemotherapy is good for some patients, but it’s not effective in all cases. Between 20 and 50% of cancer patients don’t respond to these drugs,” explained Geoff Macintyre, head of the Computational Oncology Group at the Spanish National Cancer Research Centre (CNIO). “These patients will suffer the side effects caused by chemotherapy without any clinical benefit.”
The work is published in Nature Genetics.
Avoiding unwanted chemotherapy side effects and treatment
The test is built upon the fact that many tumours accumulate changes in the number of chromosomes in their cells. One consequence, Laura Madrid, first author, explained, is that “cancer cells do not have the correct amount of genetic material.”
These chromosome changes vary in each tumour, but together, they form signatures of chromosomal instability, which the researchers then used to develop biomarkers. The biomarkers allowed the researchers to detect, in advance, patients that are resistant to chemotherapy.
The ability to precisely identify patients who will not respond to chemotherapy means avoiding unnecessary treatment and side effects, providing a sense of relief to the patients. This also helps in releasing the costly burden on healthcare systems, a significant benefit for both patients and healthcare providers.
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.”
The test was validated using data from 800 cancer patients
Once the team developed the biomarkers, they tested them using a simulated trial against existing patient data. They used a large amount of data from 840 cancer patients who either had breast, prostate, ovarian, or sarcoma cancer or who had already been treated with chemotherapy.
It was then 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 therapy the patients received.
The researchers found that the test accurately predicted resistance to treatment for three common types of chemotherapy: platinum-based, anthracycline, and taxane chemotherapy.
Additionally, 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.
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.”
We can adapt it to work alongside other genomic sequencing methods that are commonly used to personalise treatment for cancer
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 the 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.”
