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Altered Cell Behavior and Resistance in Neuroblastoma

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Researchers at Lund University in Sweden have identified one of the reasons why the childhood cancer neuroblastoma becomes resistant to chemotherapy. The findings are significant for how future treatments should be designed. The results have been published in Science Advances.

Neuroblastoma is an aggressive cancer of the sympathetic nervous system, especially of the adrenal gland. Despite intense treatment with chemotherapy, the disease can be difficult to cure and the prognosis is poor for children who have the aggressive variant. One of the reasons is that the tumour often develops resistance to drugs. In order to understand what happens when the tumour becomes resistant, good disease models are needed that can mimic the complex drug treatment given to patients today:

“Tumours from patients with neuroblastoma look very different, and it is difficult to produce a model that is representative of many patients. This type of challenge often limits medical research”, explains the study's first author, Adriana Mañas, child cancer researcher at Lund University.

However, the researchers have now succeeded in developing a model in mice with human neuroblastoma tumour cells, which makes it possible to follow the mechanisms that occur when certain tumour cells develop resistance to drugs.

“What happens is that the tumour cells change to mimic embryonic cells from the fetal development phase. These embryonic tumour cells are more resistant to chemotherapy”, says research group leader Daniel Bexell, who led the study.

It has long been known that genetic changes are crucial for neuroblastoma to form and develop into an aggressive tumour. However, when it comes to resistance, it is not primarily about genetic changes, but rather that the cells quickly adapt their behaviour. The reason why the embryonic tumour cells are less responsive to drugs is not yet fully understood, but the researchers think that that the cells in their immature state can adapt and survive in changing conditions.

“Current treatment with chemotherapy targets rapidly dividing tumour cells. Our research results can contribute to new treatments which better reach the entire tumour, in order to avoid the development of resistance. In future research, it will be important to understand how to specifically target the embryonic state of the neuroblastoma cell in order to cure patients”, concludes Daniel Bexell.

Reference: Mañas A, Aaltonen K, Andersson N, et al. Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance. Sci Adv. 2022;8(43):eabq4617. doi: 10.1126/sciadv.abq4617

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