Tumor Genome Marker May Predict Treatment Benefit in Pediatric Cancers
Posted on 27 May 2026
Relapsed pediatric solid tumors remain challenging to treat, and the benefit from targeted agents can be difficult to anticipate before therapy begins. Clinicians need indicators that predict response and help tailor enrollment in early-phase studies. Reliable biomarkers could reduce exposure to ineffective regimens in children and young adults with limited options. Researchers at the University of Birmingham have identified a potential biomarker for predicting response to a specific cancer treatment in children with Ewing sarcoma and other tumor types.
The Phase I/II treatment arm of the eSMART trial was carried out at the Cancer Research UK Clinical Trials Unit (CRCTU) and published in Clinical Cancer Research. The study identified a high aneuploidy score as a potential indicator of clinical benefit from low-dose irinotecan, a chemotherapy drug commonly used in pediatric cancers, combined with olaparib, a PARP inhibitor used in several adult cancers.
Aneuploidy, a tumor genome change marked by an abnormal number of chromosomes in a cell, was assessed to derive an aneuploidy score for each case. In a retrospective comparison of tumors from patients who did and did not benefit, those with high scores were significantly more likely to respond or achieve durable disease control. By contrast, neither Ewing sarcoma status nor gene alterations linked to faulty DNA repair correlated with treatment benefit.
The treatment arm recruited 70 patients and treated 66 across the UK, France, the Netherlands, and Spain; all had solid tumors. Thirty-six had Ewing sarcoma and 34 had other malignancies, mainly sarcoma and central nervous system tumor types such as osteosarcoma, neuroblastoma, rhabdomyosarcoma, nephroblastoma, medulloblastoma, and choroid plexus carcinoma. At enrollment, patients had relapsed several times, and a cure was not expected.
Twelve patients derived benefit from the regimen, showing partial or complete tumor shrinkage or stable disease for more than six months. This analysis marks the first association between aneuploidy score and response in a pediatric cancer trial, and the high score did not track with any single tumor type. The team noted that a high aneuploidy score could potentially emerge as a biomarker for other DNA repair inhibitor trials in pediatric cancer and expressed hope it might be applicable to adult trials.
"These are really exciting data, and we are grateful to all the patients and families who enrolled in this study. While treatment with specific DNA repair inhibitors such as PARP inhibitors is fully established in specific adult cancer types with specific gene alterations as part of standard of care treatment, we have not yet identified such specific cancer groups in pediatric cancer," said Dr. Susanne Gatz, Associate Clinical Professor in Pediatric Oncology in the Department of Cancer and Genomic sciences at the University of Birmingham.
"Having identified a high aneuploidy score as a potential biomarker for benefit to DNA repair inhibitor trials in pediatric cancers could identify such a specific cancer group. More research is needed to see if this finding can be translated to other DNA repair inhibitor trials, and to better understand the link between high aneuploidy score and treatment benefit," added Dr. Gatz.
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