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The Medical Research Council awarded Dr John Jacob upwards of £200,000 to fund a project on brain cancer modelling.

Brain cells that originate in the cerebellum give rise to the most common childhood brain tumour, known as medulloblastoma, which can also affect adults. Although it can be cured, it is often a devastating disease, with common treatment options resulting in an increased risk of adverse side effects such as strokes and seizures.

Like most cancers, the development of new treatment options that improve survival rate and reduce side effects is reliant on researchers establishing models that reflect the human tumours, in order to test the efficacy of new therapeutics before these are tested in patients. Existing models for medulloblastoma have shortcomings, making the discovery of new treatment options slow. This is due to:

  1. Growing medulloblastoma cells outside of a patient is hard, due to the change in environmental factors. Growing cells outside the body usually does not accurately reflect the microenvironment that cells are derived from, and so the cells will behave differently and unlike a real tumour. As a result, only a few cell lines from medulloblastoma patients have successfully been grown ex vivo.
  2. Models can be costly, and these include mouse-based models, which pose limitations due to the difference in species.
  3. Medullobastoma tumours are genetically different between patients – there is no 'one size fits all' model and there is a need to develop more treatment options that target specific genetic subtypes in order to improve survival.

S. John JacobIn this CARP award, Dr John Jacob aims to investigate a specific genetic subtype of medulloblastoma (known as sonic hedgehog medulloblastoma) – and test if the presence of the tumour microenvironment, which consists of non-cancerous cerebellar tissue, is necessary to better simulate the typical tumour growth conditions.

Working alongside Associate Professor Esther Becker and Dr Benjamin Schuster-Boeckler (Big Data Institute & Oxford Ludwig Cancer Institute), the team hope to recreate the in vivo tumour microenvironment more accurately compared to existing models. The Becker group previously established a methodology to grow human cerebellar neurons from human induced pluripotent stem cells (hiPSC). By using hiPSCs to form miniature cerebellar structures, termed cerebellar organoids, the tumour microenvironment can be recreated in a dish.

The team hope to overcome the existing modelling difficulties by growing medulloblastoma cells on these organoids. Dr Jacob, aided by the computational biology expertise of Dr Schuster-Boeckler will then investigate the growth of individual tumour cells, in a more physiological context. The resulting outcomes could mean the development of a new model to test patient-specific therapies on, in order to assess their toxicities and efficacy more accurately.

Dr John Jacob is a consultant neurologist who is interested in better understanding the genetic complexity of cancer and what it means for personalised treatment. Through this award and collaboration, Dr Jacob hopes to improve the success of therapy development and ultimately improve the repertoire of therapies of this cancer.

The Medical Research Council Clinical Academic Research Partnership scheme allows NHS consultants with a PhD or MD to participate in collaborative high-quality research partnerships with established leading biomedical researchers.

 

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