A test has been discovered that predicts which patients will not respond to cancer chemotherapy.

Targeted therapies are already a reality in cancer treatment. A weak point in tumor cells is discovered, and a drug is sought or developed that effectively treats it. But just as important as knowing what will work is ruling out what won't work and will only cause side effects. Along these lines, a group of researchers from the Spanish National Cancer Research Centre (CNIO) has developed a method that predicts which patients will find standard, commonly used chemotherapy treatments, based on compounds containing platinum, taxanes, and anthracyclines, ineffective . The work is published in Nature Genetics.

Chemotherapy, which has been a standard cancer treatment for decades, seeks to destroy tumor cells using drugs. However, it is not always effective. "Chemotherapy is good for some patients, but it is not effective in all cases. Between 20% and 50% of cancer patients do not 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 side effects caused by chemotherapy, without any clinical benefit," he adds.

The team is led by Macintyre, in collaboration with the University of Cambridge and the spin-off company Tailor Bio. "We've found a way to implement precision medicine with standard chemotherapies ," says Macintyre, who worked with researchers Joe Sneath Thompson and Bárbara Hernando, from CNIO, and Laura Madrid, from Tailor Bio, as first authors.

"Importantly, our study introduces biomarkers that allow for patient stratification when multiple chemotherapies not originally developed as targeted therapies are used," they write in Nature Genetics.

"We've developed a genomic test that allows three standard chemotherapies to be used in a targeted manner, that is, in patients we know will respond to them," Thompson explains. " This test can be applied to different types of cancer ; our results could benefit hundreds of thousands of patients each year."

The method developed by the CNIO team is based on the fact that many tumors accumulate alterations or changes in the number of chromosomes in their cells. One consequence, explains Laura Madrid, is that "cancer cells do not have the appropriate amount of genetic material."

These alterations vary in each tumor, so that together they form a characteristic pattern, a signature of chromosomal instability. The study now published develops biomarkers based on these signatures of chromosomal instability.

These biomarkers allow us to "detect early which patients are resistant to these treatments so we can choose alternative, more effective treatments, thereby avoiding unnecessary side effects," explains Macintyre.

The precise use of chemotherapy benefits not only patients but the system as a whole, as it reduces healthcare costs by reducing the cost of ineffective therapies and treating complications related to therapy side effects.

Once the biomarkers were developed, the CNIO team tested them in an innovative way: with a simulated trial, that is, with existing data. The authors drew on a large amount of data from cancer patients who had already been treated with the chemotherapies analyzed in the study.

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 says. They were able to demonstrate the efficacy of the resistance biomarkers they propose against one of the three types of chemotherapy evaluated—based on platinum compounds, taxanes, and anthracyclines.

To bring this knowledge to the clinic, the technology developed by CNIO researchers must now be validated in a hospital setting . The group has already received funding for this from the Ministry of Digital Transformation and the Civil Service. This project, in collaboration with the spin-off company Tailor Bio and the 12 de Octubre University Hospital (H12O), will evaluate the technology's integration into the healthcare system by analyzing already available 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 straightforward. But with persistence and collaboration, it's possible to turn a research project into a truly clinically promising technology ," says Macintyre.