CRIG researchers from the group of Prof. Frank Speleman and Prof. Kaat Durinck discover promising combination treatment for neuroblastoma
Neuroblastoma is a pediatric tumor originating from the sympathetic nervous system with current survival rates for high-risk cases still being disappointingly low. Typically there is only a low mutation load, but DNA copy number changes are highly recurrent. Analysis of these recurrent somatic DNA copy number variants allows to identify important drivers of neuroblastoma development.
CRIG researchers from the group of Prof. Frank Speleman and Prof. Kaat Durinck have used this approach to identify and characterize a new neuroblastoma dependency factor called ribonucleotide reductase subunit M2 (RRM2). RRM2 is the catalytic component of the RNR enzyme and is essential for the maintenance of deoxynucleotide triphosphate (dNTP) pool homeostasis required for DNA replication and repair. Via cell culture, zebrafish and mouse experiments, combined with bioinformatical analyses, the researchers could show that RRM2 depletion rapidly leads to increased levels of replicative stress due to DNA replication fork stalling and decreased cell proliferation.
Moreover, they showed that this replicative stress activates a CHK1 based DNA damage response, and therefore increases the sensitivity of neuroblastoma cells to pharmacological CHK1 targeting. Combining Prexasertib treatment (CHK1 inhibitor) with Triapine (RRM2 inhibitor) gave promising results in their preclinical models, and will now be further investigated as a treatment for both high risk neuroblastoma as other pediatric cancers.
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Read the original press release (in Dutch) via this link.
The news was also picked up by various national news services, like 'Het Nieuwsblad'.