Chemotherapy seeks to destroy tumor cells and has been a standard treatment for cancer for decades. However, it doesn't always work. "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," explains 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 team led by Macintyre, in collaboration with the University of Cambridge and Cambridge-based startup company Tailor Bio, has developed a method that predicts which patients will not respond to commonly used chemotherapy drugs, such as platinum-, taxane- and anthracycline-based chemotherapies.
"We have found a way to turn conventional chemotherapies into precision medicines" says Macintyre. The work is published in Nature Genetics, with CNIO researchers Joe Sneath Thompson and Barbara Hernando, and Tailor Bio's Laura Madrid as first authors.
"Importantly, our study introduces biomarkers for patient stratification for multiple medicines that were not originally developed as targeted therapies", say the authors in Nature Genetics.
"Our genomic test quantifies biomarkers for the targeted use of three chemotherapies", Thompson explains. "This test can be applied to many different types of cancer, and therefore, our results could benefit hundreds of thousands of patients each year."
Recognizing each tumor through chromosome changes
The method developed by the CNIO team is based on the fact that many tumors accumulate changes in the number of chromosomes in their cells. One consequence, Laura Madrid explains, is that "cancer cells do not have the correct amount of genetic material."
These chromosome changes vary in each tumor, but together they form characteristic patterns, or signatures of chromosomal instability. The study now published develops biomarkers based on these signatures of chromosomal instability.
These biomarkers allow us to "detect in advance which patients are resistant to these treatments so that they can avoid unnecessary side effects", explains Macintyre.
The precise use of chemotherapy benefits not only patients but the healthcare system as well by avoiding the cost of unnecessary treatment and complications related to therapy side effects.
Validated with data from more than 800 patients
Once the biomarkers were developed, the CNIO team tested them in an innovative way: with a simulated trial, that is, with existing patient data. The authors drew on a large amount of data from cancer patients who had already been treated with the chemotherapies.
Specifically, the group worked with data from 840 patients with different types of cancer. "We used data from patients with breast, prostate, ovarian, and sarcoma cancer," Hernando explains. "We were able to demonstrate the efficacy of our resistance biomarkers for three types of chemotherapy: platinum compounds, taxanes, and anthracyclines". Following the success of this study, work has already begun on developing further tests for targeted therapies to see how widely the technology could be applied.
This study has been made possible thanks to the support of the Carlos III Health Institute, the Ministry of Science and Innovation, Cancer Research UK, and the "la Caixa" Foundation.
Further funding to bring this technology to the clinic
To bring this knowledge to the clinic, the technology must now be validated in a hospital setting.
The group has already received funding for this purpose from the Ministry for Digital Transformation and Public Service. This project, in collaboration with Tailor Bio and the 12 de Octubre University Hospital (H12O), will evaluate the technology's integration into the healthcare system by analyzing existing patient samples. This will demonstrate that the technology is ready for use in clinical trials by 2026.
"Taking a biomarker from the discovery phase to the clinic is rarely easy. But with persistence and collaboration, it's possible to turn a research project into a truly promising technology," says Macintyre.
Funding for this new validation study has been provided by the European Union through the Recovery and Resilience Facility, NextGenerationEU funds, and the Recovery, Transformation, and Resilience Plan (Component 16, Reform 1), Ministry for Digital Transformation and Public Service.
About the Spanish National Cancer Research Center (CNIO)
The Spanish National Cancer Research Center (CNIO) is a public research center under the Ministry of Science, Innovation and Universities. It is the largest cancer research center in Spain and one of the main ones in Europe. It hosts half a thousand scientists plus support staff, dedicated to improving the prevention, diagnosis and treatment of cancer.
