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Published on: December 9, 2015
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Predicting resistance to chemotherapy using chromosomal instability signatures.
Joe Sneath Thompson1,2, Laura Madrid2, Barbara Hernando1
1Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
Nature Genetics
|June 23, 2025
Summary
Chromosomal instability signatures can predict chemotherapy resistance, enabling personalized cancer treatment. This genomic test identifies patients unlikely to benefit from platinum, taxane, or anthracycline drugs, avoiding toxic side effects.
Area of Science:
- Genomics
- Oncology
- Biomarker Discovery
Background:
- Chemotherapies lack precision biomarkers, leading to patient exposure to toxic side effects without guaranteed efficacy.
- Current treatment paradigms often employ a one-size-fits-all approach to chemotherapy administration.
Purpose of the Study:
- To develop and validate chromosomal instability (CIN) signature biomarkers for predicting resistance to platinum-, taxane-, and anthracycline-based chemotherapies.
- To assess the clinical utility of CIN signatures in diverse cancer types and treatment regimens.
Main Methods:
- Retrospective analysis of real-world cohorts (n=840) using emulated randomized-control biomarker clinical trials.
- Validation of predictive capacity through nonrandomized emulations for specific drug-cancer type combinations.
- Demonstration of feasibility using whole-genome sequencing, capture-panel sequencing, and cell-free DNA.
Main Results:
- CIN signatures predicted elevated treatment failure risk for taxane and anthracycline in ovarian, metastatic breast, and metastatic prostate cancers.
- Predictive capacity for platinum resistance in ovarian and anthracycline resistance in sarcoma was also demonstrated.
- Hazard ratios (HR) ranged from 1.46 to 7.44, indicating significant associations between CIN signatures and treatment resistance.
Conclusions:
- Chromosomal instability signatures are valuable biomarkers for predicting chemotherapy resistance across multiple cancer types.
- These findings support the potential to transition from a one-size-fits-all chemotherapy approach to precise, tailored cancer treatments.
- Genomic testing for CIN signatures offers a pathway to optimize chemotherapy selection and minimize patient toxicity.
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