Cancer is the leading cause of disease-related death in childhood.

This is in part due to cancer-associated genes called oncogenes that can be found far from chromosomes in cell nuclei on ring-shaped DNA inside tumour cells.

Circular extra-chromosomal DNA elements (ecDNA) are pieces of DNA that have broken off normal chromosomes and then been wrongly stitched together by DNA repair mechanisms.

This phenomenon leads to circular DNA elements floating around in a cancer cell.

“We have shown that these ecDNAs are much more abundant in solid paediatric tumours than we previously thought,” said Lukas Chavez, PhD, an associate professor in the Cancer Genome and Epigenetics Programme at Sanford Burnham Prebys.

“And we have also shown that they are associated with very poor outcomes.”

An international team of scientists published findings August 7, 2025, in Cancer Discovery helping to explain why a common form of paediatric cancer called neuroblastoma is often treated successfully with chemotherapy but prone to relapse in several years.

Cancer cells with many copies of the MYCN oncogene on ecDNA grow quickly but are more easily destroyed by chemotherapy.

Tumour cells with fewer copies of the oncogene located on ecDNA enter a zombie-like state known as senescence where they persist but no longer divide to make new cells.

These zombie cells are unaffected by chemotherapy and can be reactivated a year or two later, triggering the cancer to relapse.

The researchers demonstrated that combining standard chemotherapy with a secondary therapy able to target senescent cancer cells led to dramatically improved outcomes in tests on mouse models of neuroblastoma.

Ashley Hui, a graduate student in the Chavez lab, contributed to this study by showing that the phenomenon of zombie cells with low amounts of ecDNA carrying MYCN can also be observed in medulloblastoma, the most common malignant brain tumour type in children.

“By integrating genomic analyses of tumour DNA with hypothesis-driven functional experiments and high-throughput drug screening, we aim to discover new drugs and drug combinations that halt tumour growth by eliminating these oncogenic DNA circles,” said Chavez, a co-author of the study.

“Ultimately, our goal is to translate these scientific advances into more effective therapies and lasting cures for children with brain cancer.”

Source: Sanford Burnham Prebys