Cloning or twinning: new methods to eradicate neuroblastoma!

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Despite the current intensive treatments, the chances of survival for children with neuroblastoma that has come back (in relapse) remain unacceptably low, with less than 20% of children achieving a long-term cure while the treatment causes severe long-term side effects for survivors.

As a result, today’s challenge is to reduce the side effects of the treatment while retaining and improving its efficacy to cure more patients.

An international team of computer scientists, biologists, and clinicians will collaborate to build computer models of patients (Digital Twins), which will allow the design of personalised therapies that are more efficient and less toxic than the current therapies.

The technique of digital Twins is already successfully used in engineering, where engineers build, test, and improve a computer model so that they can build the best version of the real machine.

The team will start by building “DigiTwins” of mouse models with neuroblastoma. These mouse models are very similar to the human disease and have been successfully used to develop and test new drugs for neuroblastoma. They allow to perform a comprehensive molecular analysis, where changes in the genome, in the expression of genes (epigenetics), in the production of proteins and of metabolites (which supply building blocks for the body) will be measured. The team will then use advanced computational methods to combine these molecular data and construct the Digital Twin models. Every neuroblastoma mouse will have a corresponding DigiTwin computer model, which can be used to try out different treatments virtually on the computer so that the best possible individual treatment can be identified. These treatments then will be tested in the mice.

Once the accuracy of the DigiTwin models in mice is ascertained, it will be translated to humans. The accuracy of these human DigiTwin models will be evaluated against the treatment outcomes of these patients.

The final objective of DigiTwins project is to pave the way for future clinical studies, where DigiTwins can provide better and more personalised treatments for neuroblastoma patients.