Why some “lower-risk” childhood cancers turn deadly
Scientists have uncovered hidden aggressive cancer cells in children whose tumors were previously considered lower risk, revealing why some cases of rhabdomyosarcoma become unexpectedly deadly. The discovery could help doctors identify dangerous tumors earlier and develop personalized treatments that improve survival while reducing unnecessary chemotherapy.
Key points
- Some childhood tumors classed as lower risk contain hidden aggressive cancer cells, researchers found.
- The study examined rhabdomyosarcoma samples from 16 children, including four fatal fusion-negative cases.
- Scientists say a shared aggressive cell state may matter more than a single genetic marker.
Scientists have found that some childhood cancers classified as lower risk can contain hidden populations of highly aggressive cells, which may explain why some children fare badly despite lacking the usual genetic warning signs. The findings, published in Cancer Research, come from researchers at the Wellcome Sanger Institute, the University of Cambridge, Great Ormond Street Hospital, University College London and collaborating institutions.
The work focused on rhabdomyosarcoma, a cancer that develops from muscle tissue and is among the most common soft tissue cancers in children under 15. About 55 children are diagnosed with it in the United Kingdom each year.
How the tumors were studied
Doctors usually split rhabdomyosarcoma into two groups based on whether a tumor carries a genetic fusion marker linked to especially aggressive disease. Children with the fusion have substantially lower survival rates, but some children without it still develop fatal cancers.
The team compared tumor samples from 16 children, including four whose cancers lacked the fusion marker but proved fatal. Using single-cell RNA sequencing and spatial transcriptomics, they found that some non-high-risk tumors contained cells whose gene activity closely resembled that of high-risk tumors, reached through different rare genetic changes.
By studying tumors one cell at a time, we uncovered hidden populations of aggressive cancer cells that conventional methods miss.
— Dr. Karin Straathof
What researchers said
Dr. Karin Straathof of UCL Cancer Institute and GOSH said studying tumors one cell at a time revealed hidden aggressive cell populations that conventional methods miss. Professor Sam Behjati, formerly at the Wellcome Sanger Institute, said the work shows an overarching cell state of aggressive disease that defies conventional classification.
The researchers say the findings could eventually help identify children at greater risk and spare others unnecessary intensive treatment, but further research is needed before routine clinical care changes. They are now expanding the work to hundreds more tumor samples.
