New DNA test can determine if chemotherapy will fail before first dose

Most cancer patients still receive the same chemotherapy their grandparents would recognize, without a test to guide it. The drugs can shrink tumors, yet they also batter healthy tissue and leave many people sicker without ever halting the disease.

A new DNA test promises to flag who is unlikely to benefit before the first infusion, letting doctors steer those patients to other options, a shift long urged because between 20 % and 50 % of people gain no real advantage from conventional regimens.

The study behind the test is led by Geoff Macintyre, a computational oncologist at the Spanish National Cancer Research Centre (CNIO), working with colleagues at the University of Cambridge and the start‑up Tailor Bio.

Chemotherapy’s uneven track record

Many cytotoxic drugs entered clinics decades ago, well before the modern push for companion diagnostics, so they get prescribed “one size fits all,” even though tumor biology varies wildly.

Patients who do not respond endure nausea, neuropathy, and hair loss with no payoff, while healthcare systems pay for cycles that were doomed from the start.

Oncologists have had a few molecular guides, such as hormone‑receptor status or the OncotypeDX breast recurrence score, yet most solid tumors still rely on guesswork when it comes to taxanes, platinum salts, or anthracyclines.

DNA helps test chemotherapy resistance

The new approach zeroes in on chromosomal instability, a hallmark of cancer in which cells gain or lose whole DNA chunks and end up with scrambled genomes.

Such chaos is not random, though, and researchers have teased out patterns, or “signatures,” that correlate with how tumors react to different stresses.

Macintyre’s team built a library of 17 signatures from thousands of archived tumor genomes, then matched them against drug outcomes.

Three stood out: one flagging platinum resistance, another tied to taxane evasion, and a trio linked with anthracycline failure.

New test predicts chemotherapy failure

Doctors need only a standard biopsy or, for roughly one‑third of ovarian cases in the pilot, a blood sample carrying tumor DNA.

Low‑coverage whole‑genome sequencing maps copy‑number changes, software scores the signatures, and an algorithm labels the sample “sensitive” or “resistant” for each drug.

“We’ve found a way to turn conventional chemotherapies into precision medicines,” said Macintyre, pointing out that the assay measures all three drugs at once, so a single readout can steer first‑, second‑, and third‑line choices.

Chemotherapy failure and DNA patterns

The study analyzed records from 840 people with breast, prostate, ovarian, or sarcoma tumors and retrospectively emulated randomized trials.

Those whom the test predicted as taxane-resistant failed chemotherapy treatment up to seven times faster than predicted-sensitive patients, while platinum-flagged ovarian cases relapsed 45% sooner.

The work then moved to a real‑world pilot at Cambridge’s OV04 cohort, where fresh sequencing and clinical follow‑up confirmed the patterns.

Again, predicted resistant groups progressed significantly sooner, despite receiving state‑of‑the‑art care.

Benefits for patients and health systems

Avoiding futile chemotherapy shields people from toxicity and opens the door to immunotherapy, targeted agents, or clinical trials sooner.

Fewer complications mean shorter hospital stays and less supportive medication, easing both personal and financial burdens.

At scale, the model could save hundreds of millions of dollars each year, because expensive infusions and their downstream side effects would no longer be administered on hope alone.

Steps toward clinical use

Because most hospitals already run large gene panels, the team checked whether their signatures survive when data come from an Illumina TruSight Oncology 500 assay, a regulatory‑cleared panel common in pathology labs.

In 93 % of paired samples, the panel and whole‑genome calls agreed on drug sensitivity, suggesting the pipeline can slot into existing workflows.

A Spanish ministry grant now funds validation at Madrid’s 12 de Octubre University Hospital, aiming to prove the test is ready for prospective trials by 2026.

Test could guide chemotherapy decisions

The study relied on retrospective data and emulated trials using the test, so randomized prospective chemotherapy evidence is still needed, especially for sarcoma, where sample sizes were small.

Regulatory pathways for test-based diagnostics that guide already-approved chemotherapy drugs can be tricky, because no drug company sponsors the effort.

Another challenge is tumor heterogeneity, as a single biopsy may miss resistant clones. Liquid biopsy helps, yet only when enough circulating DNA is present, which varies with cancer type and stage.

If upcoming trials confirm performance, oncologists could soon click a software button and know, before prescribing, whether the standard drug cocktail will likely fail.

That knowledge would transform chemotherapy from educated guess to informed decision, sparing patients needless harm and giving every infusion a better chance to matter.

The study is published in Nature Genetics.

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