Institute of Cancer Research study identifies blood-based marker of chemotherapy resistance in advanced prostate cancer

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(IN BRIEF) The Institute of Cancer Research has led a study showing that chromosomal instability in circulating tumour cells can predict resistance to cabazitaxel in men with advanced prostate cancer. Using blood samples from more than 200 patients enrolled in the CARD trial, researchers found that high chromosomal instability was linked to significantly worse survival and no additional benefit from chemotherapy compared with switching hormone-targeting treatments. The findings suggest that a simple blood test could help clinicians personalise treatment decisions, avoid unnecessary chemotherapy toxicity, and guide patients toward more effective options or clinical trials. The study was funded by Sanofi and published in JCI Insight.

(PRESS RELEASE) LONDON, 22-Dec-2025 — /EuropaWire/ — The Institute of Cancer Research has led new research identifying a potential way to predict resistance to cabazitaxel, a chemotherapy drug commonly used to treat advanced prostate cancer. By analysing blood samples from more than 200 men, the study found a strong link between chromosomal instability in circulating tumour cells (CTCs) and poorer clinical outcomes among patients with metastatic castration-resistant prostate cancer (mCRPC).

The findings indicate that chromosomal instability measured in CTCs can predict both overall survival and tumour response to treatment. Crucially, the research shows that this biological marker can be assessed using feasible laboratory techniques, overcoming the limitations of existing methods that are impractical for routine clinical use. The results suggest that some patients may be exposed to the side effects of chemotherapy without deriving meaningful benefit.

Chromosomal instability describes the disruption of normal chromosome structure or number caused by abnormal cell division and has long been associated with aggressive cancer behaviour. In this study, researchers demonstrated that evaluating chromosomal instability in tumour cells circulating in the bloodstream provides clinically relevant insight into treatment resistance. This could allow doctors to identify patients who are unlikely to benefit from cabazitaxel and guide them toward alternative therapeutic strategies.

The research builds on samples collected from participants in the CARD trial, a large European study involving more than 60 sites across 13 countries. All patients had mCRPC, had previously received docetaxel chemotherapy, and had experienced disease progression within 12 months of treatment with an androgen receptor pathway inhibitor. While the CARD trial established cabazitaxel as the preferred option over switching hormone-targeting therapies for many patients, the new analysis highlights important differences in individual response.

To conduct the study, researchers isolated rare circulating tumour cells from blood samples using a non-enrichment approach. After removing red blood cells and applying fluorescent staining, semi-automated analysis was used to identify CTCs among white blood cells. A proprietary algorithm based on cell morphology was then applied to classify tumour cells as chromosomally stable or unstable. Samples were collected at baseline, after two treatment cycles, and at the end of therapy.

The results revealed a clear distinction between patient groups. Men with low chromosomal instability had a median overall survival of approximately 15 months, compared with just under nine months for those with high instability. Importantly, in patients with high chromosomal instability, cabazitaxel did not outperform a switch to another hormone-targeting therapy, indicating a lack of added benefit from chemotherapy.

By enabling chromosomal instability to be assessed through a simple blood test, this approach avoids invasive biopsies and provides real-time insight into tumour biology at key decision points in treatment. The researchers note that this could support more personalised care, reduce exposure to ineffective chemotherapy, and help identify patients who may benefit from clinical trials testing alternative treatments.

The study was funded by Sanofi and published in JCI Insight. Further validation will be required, but the findings represent a significant step toward integrating liquid biopsy-based biomarkers into clinical decision-making for advanced prostate cancer.

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SOURCE: The Institute of Cancer Research