Funded by The Little Princess Trust and administered by CCLG
Lead investigator: Prof Steve Clifford, Newcastle University
Award: £1,053,350.00
Awarded June 2021
Medulloblastoma is the most common malignant brain tumour of childhood. Over the last 50 years, advances in standard treatments (i.e. surgical removal of tumour, radiotherapy and chemotherapy) have led to long-term survival rates of approximately 70%.
We have identified biologically-defined groups of the disease which do not respond to current therapies (e.g. MYC-driven medulloblastoma which has less than 10% survival). Moreover, medulloblastoma comes back (disease relapse) in 30% of patients and this is often driven by the gene 'MYC', and is usually fatal.
Together, these groups of 'MYC-driven' medulloblastomas account for a high proportion (10%) of all childhood cancer deaths, and therefore present some of the most significant unmet clinical challenges in paediatric oncology.
To address this challenge, and minimise the chance of treatment-resistance, we will combine two different treatment approaches; drugs which indirectly target MYC (MYC-targeting), and a type of immune therapy, Chimeric Antigen Receptor T-cells (CARTs), which is also designed to target MYC-driven medulloblastoma. We have already successfully established both of these treatments individually in our models of MYC-driven medulloblastoma, and will now test them together in an expanded strategy.
Our preclinical combination treatment trials will deliver the essential evidence to progress these treatments into human clinical trials. These preclinical trials will track how tumours respond to treatment, identifying potential mechanisms oftreatment resistance.To deliver this critical project we have brought together childhood brain tumour expertise from three internationally-leading research institutes (Institute for Cancer Research (ICR), Newcastle University Centre or Cancer (NUCC) and UCL Great Ormond Street Institute of Child Health (ICH)).
Our collective expertise intreatment-resistant and relapsed medulloblastoma, which encompasses resources in disease biology, mouse models and the development of new treatment approaches, positions us ideally to address this unmet need, and deliver therapies to the clinic which will lead to patient benefit.