Identifying molecular mechanisms and therapeutic targets in childhood neural tumors

Medulloblastoma and Neuroblastoma are among the most common neural tumors in children. Neural tumors constitute around one third of all childhood cancers, but almost half of the mortalities.

In Sweden most children affected by cancer survives, however, many survivors experience late complications in life, with one third getting life threatening conditions including secondary cancers, heart failure, and stroke.

Taken together, this shows not only a need for increasing our understanding of molecular mechanisms operating during neural tumor formation, but furthermore, it highlights the importance of developing targeted therapies that will spare the developing child while specifically eradicating tumor cells.

To achieve this, we have developed new cancer models using human disease-relevant cell types.

By somatic cell reprogramming to induced pluripotent stem (iPS) cells and differentiation to neural stem cells, we have generated new orthotopic cancer models with cells from patients with familial driver mutations known to cause medulloblastoma and neuroblastoma. We show that our models mimic the human disease on histology and transcriptome.

Using our new models, we aim to understand molecular mechanisms important for tumor initiation and progression, identify tumor-specific targets for precision medicine, and for screening and testing purposes. Our studies will provide better models where therapeutics can be discovered and evaluated.