SPOTLIGHT ON DR MANAV PATHANIA
Department of Oncology, University of Cambridge
CRUK Children’s Brain Tumour Centre of Excellence
Milner Therapeutics Institute
Research focus: We investigate the most aggressive types of brain tumours in children and young adults. These tumours often arise from specific neural progenitor cells that accrue mutations during foetal brain development. There are numerous combinations of mutations that must occur together for tumours to form, and different sets of mutations associate with different age groups and anatomical locations in the brain— giving rise to different tumour “subtypes”. We model these mutations in embryonic mice and develop representations of the different tumour subtypes, which we then use for investigating precision therapy approaches and interactions between tumour cells and normal cells, and how these are co-opted into helping tumours grow and evade treatments.
Manav Pathania
Recent advance from the lab: We recently developed 16 mouse models of paediatric high-grade gliomas, representing a significant proportion of the genetic diversity of this disease. We used these models to identify targeted therapy approaches in a preclinical setting (McNicholas et al. Cancer Discovery (2023)).
Key challenge for the field: Brain tumours are the number one cause of cancer-related death in the under 40 age bracket, and the most common cancer in children 14 years old or younger. However, despite these statistics their overall numbers are much lower than other types of adult or geriatric cancers, meaning that cancer in children and adolescents is rare. Due to the smaller market size they represent, there is less incentive to develop new therapies for brain tumours. Unfortunately, this has contributed to a very dismal rate of improvement in survival over the decades, with no new effective treatments, especially for those diagnosed with the most aggressive brain tumours. For these children, the survival rate is essentially zero, with no children surviving 5-10 years post-diagnosis. The impact of brain tumours on families is immense and objectively, the number of years lost to disease if lives had not been cut short so prematurely is vast. Another significant challenge is the genetic heterogeneity of malignant brain tumours, which harbour many different combinations of mutations and associate with different age groups and anatomical sites within the brain. Both their rarity, and their genetic and anatomical heterogeneity, makes paediatric and adolescent brain tumours an extremely challenging area to work in, but new advancements in their treatment are desperately needed.
Most exciting basic or clinical breakthrough in the past few years: Immuno-oncology is providing new hope for treating previously intractable cancers and have shown promise in high-grade brain tumours in children. Our mouse models are the only syngeneically engraftable models of this disease. We hope that they can be useful for investigating how tumour cells evade immune surveillance, and for evaluating new immuno-oncology approaches that can remobilise the immune system against brain tumours.
Published July 2024