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 the adrenal gland. Despite intensive treatment with chemotherapy, the disease can be difficult to cure and the prognosis is poor for children with the aggressive variant. One reason is that the tumor often develops drug resistance. To understand what happens when the tumor becomes resistant, good disease models are needed that can mimic the complex drug treatment given to patients today:
Tumors 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.”
Adriana Mañas, first author of the study, childhood cancer researcher at Lund University
However, researchers have now managed to develop a model in mice with human neuroblastoma tumor cells, which makes it possible to follow the mechanisms that occur when certain tumor cells develop resistance to drugs.
“What happens is that the tumor cells change to mimic the embryonic cells of the fetal development phase. These embryonic tumor cells are more resistant to chemotherapy,” says research group leader Daniel Bexell, who directed the study.
It has long been known that genetic changes are crucial for neuroblastoma to form and become an aggressive tumor. However, when it comes to resistance, it is not mainly genetic changes, but cells quickly adapting their behavior. The reason why embryonic tumor cells respond less to drugs is still not fully understood, but researchers think that the cells in their immature state can adapt and survive in changing conditions.
“Current chemotherapy treatment targets rapidly dividing tumor cells. The results of our research may contribute to new treatments that better reach the entire tumor, to prevent the development of resistance. In future research, it will be important to understand how to specifically target the tumor embryonic state of the neuroblastoma cell to cure patients”, concludes Daniel Bexell.
Source:
Journal reference:
Mañas, A., et al. (2022) Clinically relevant treatment of PDX models reveals patterns of neuroblastoma chemoresistance. Advances in Science. doi.org/10.1126/sciadv.abq4617.