Researchers Identify Cause Of Childhood Cancer Agression And Treatment Possibility
Researchers have uncovered new clues about why the childhood cancer rhabdomyosarcoma (RMS) may become aggressive and possible means of treatment. Some children diagnosed with rhabdomyosarcoma (RMS) appear to have lowerrisk disease, yet their cancer can still become dangerously aggressive.
Researchers have now uncovered biological similarities that may explain why, raising the possibility of identifying these children earlier and matching treatment more closely to their actual risk. The research, which resulf was published in Cancer Research, was undertaken by a team from the Wellcome Sanger Institute, the University of Cambridge, Great Ormond Street Hospital (GOSH), University College London, and collaborating institutions.
They investigated the genetic forces behind RMS, an aggressive cancer that develops from muscle tissue. RMS is among the most common soft tissue cancers in children younger than 15, with about 55 cases diagnosed in the UK each year. Childhood cancers differ from many cancers that develop in adults.
Rather than being strongly associated with aging or environmental exposures, they commonly arise from developmental changes that increase the likelihood of cancer forming. RMS is generally divided into two major groups based on whether a tumor carries a particular genetic risk marker. That marker forms when two genes that are normally separate become fused together.
Children whose tumors contain this fusion have substantially poorer survival than those without it, even with intensive treatment. But the usual classification does not explain every case. Some children whose tumors lack this high-risk marker nevertheless develop aggressive disease, leaving researchers with the question of what drives those cancers.
The researchers set out to investigate what distinguishes these aggressive cancers in patients who had initially been categorised as non-high-risk. They compared tumours from children with highrisk and non-high-risk RMS using genomic techniques that allowed them to examine cancer cells in much greater detail.
One method, single-cell RNA sequencing, measures gene activity separately in individual cells rather than averaging signals across an entire tumor. That approach exposed aggressive cancer cells hidden within tumors that conventional classification had labeled non-high-risk. The researchers also used spatial transcriptomics, a technique that preserves information about where cells are positioned inside tissue while measuring their gene activity.
This allowed them to see how aggressive cell populations were arranged throughout the tumors. The results showed that aggressive tumours from children classified as nonhigh-risk had patterns of gene activity closely resembling those found in high-risk tumours, even though they did not carry the established genetic risk marker.
The researchers also identified rare genetic alterations in aggressive nonhigh-risk tumors that disrupted the same cellular pathways affected in high-risk disease. This indicates that different genetic changes can ultimately lead cancer cells toward a similar aggressive state.
Finding distinctive markers on these highrisk cells could eventually help researchers develop more targeted treatments. Possible approaches include immunotherapies such as CAR-T cell therapy, which could potentially attack cancer cells more selectively while limiting some of the side effects associated with conventional chemotherapy.
The researchers also hope the findings could eventually improve how children are classified at diagnosis. More accurate identification of aggressive tumors could allow clinicians to intensify treatment for patients most likely to relapse while sparing genuinely lower-risk patients from unnecessary treatment toxicity.
