New paediatric cancer marker, new hope for a treatment target

28 Feb 2024
New paediatric cancer marker, new hope for a treatment target

Researchers have newly identified a universal, essential biomarker for the childhood cancer neuroblastoma – and a potential new target for treatment.

Neuroblastoma accounts for 15% of all paediatric cancer deaths and is the most common source of childhood tumors outside of brain cancer.

The disease develops in early nerve tissue, usually in and around the adrenal glands, and typically affects children under age five.

High-risk cases have a five-year survival rate of just 50%.

Led by UC San Francisco, researchers suspected the oncoprotein AF1q, which is known to play a role in leukaemia and solid tumour progression, might be important in tumours of neural origin too.

They used the Broad Institute’s Cancer Cell Line Encyclopedia database to compare AF1q gene expression – that is, whether and how the gene is used to make cancer proteins – in 37 different types of paediatric and adult malignancies. 

The researchers also used the “Depmap” Cancer Dependency Map database to analyse the impact of gene silencing (i.e. preventing gene expression) and gene editing of different cancer cell lines. 

AF1q, they found, was expressed at the highest levels in neuroblastoma compared to all other tumour types.

Neuroblastoma cells were also more reliant upon AF1q than any other cell line.

And when they silenced AF1q in neuroblastoma cells, it appeared to initiate cell death and weaken the progress of tumours.

Results were published in Oncogene.

The key to how AF1q works in neuroblastoma, said Julie Saba, MD, UCSF paediatric oncologist and senior study author, appears to be its ability to maintain high cellular levels of N-myc, another oncoprotein which is linked to high-risk neuroblastoma. 

“N-myc has long been considered an ‘undruggable’ target in neuroblastoma,” Saba said.

“But now we see AF1q as a potential Achilles heel we can use to destabilise that target.” 

Future studies will focus on determining how AF1q interacts with other cellular proteins and then using that information to target AF1q’s actions in cancer cells.

Source: University of California - San Francisco