New Drug Targets For Childhood Cancer Neuroblastoma Identified

All neuroblastomas arise from developmental cells not normally found in children, making them a promising target for drug development

The largest single cell study to date of the childhood cancer, neuroblastoma, has answered important questions about the genesis of the disease. The researchers from the Wellcome Sanger Institute, Great Ormond Street Hospital (GOSH) and their collaborators, discovered that all neuroblastomas arise from a single type of embryonic cell called sympathoblasts.

The study, published today (5 February 2021) in Science Advances, sought to understand why neuroblastomas range in severity, with some easy to treat and others having relatively low five-year survival rates. The fact that all neuroblastomas arise from sympathoblasts makes them an attractive drug target, because these cells exist only in the tumour after the child is born.

Neuroblastoma is a rare cancer that generally affects children under five years old. It begins in the abdomen, usually in the adrenal glands – hormone-producing glands above the kidneys. Neuroblastoma is remarkable in that its severity can vary greatly between individuals. In some children the cancer will disappear without treatment, whereas in others the cancer is relentless. The five-year survival rate for neuroblastoma is one of the lowest of all childhood cancers*.

This varied outlook prompted the researchers to ask whether the range of severity could be caused by neuroblastomas arising from different cell types at different stages of the child’s development in the womb. This was made possible by the advent of single cell mRNA sequencing, a high-resolution technology that can identify different cell types present in a tissue according to the genes expressed by individual cells.

In this study, gene expression of 19,723 cancer cells was analysed and compared to a reference of 57,972 developmental adrenal cells in the hope of identifying the cell types from which neuroblastomas arise and to find novel treatment targets.