Targeting non-dividing cells in childhood high-grade tumours
Fast facts
Official title: TANGENTIAL: Targeting cellular senescence against childhood high-grade glioma
Lead researcher: Professor Juan Pedro Martinez-Barbera
Where: University College London
When: October 2023 – September 2028
Cost: £1.5 million over 5 years
Research type: Paediatric, Gliomas (High grade), Academic, Quest for cures
Grant round: Quest for cures
Paediatric Diffuse High Grade Gliomas (PDHGGs) are a collection of aggressive, fast-growing brain tumours found in children and young adults.
This group of tumours are difficult to treat as they grow and spread very quickly. Furthermore, the structure of these tumours are “diffuse”, which means that instead of growing as one, solid tumour mass, they grow and spread into surrounding brain tissue, making them very complicated to remove surgically. The prognosis for children diagnosed with these tumour is poor, with a 5 year survival rate less than 20%.
What is it?
Tumours are made of a mixture of rapidly dividing cells and non-dividing cells. These non-dividing cells, known as senescent cells, remain alive but are unable to multiply. Whilst the majority of treatments developed for cancer aim to destroy rapidly dividing cancer cells, this project is studying the role of senescent cells in PDHGG tumour formation and relapse, with a goal of developing novel drugs that could aid current treatments.
Prof. Martinez-Barbera has collaborated with researchers from several institutions to create a multidisciplinary team. Data from their previous work shows that these senescent cells can actually encourage tumour development by releasing chemicals that stimulate the growth of cancer cells. Radiotherapy and chemotherapy tend to be ineffective at removing senescent cells, so they are able to persist in the tumour site and encourage tumour growth. Furthermore, recurrence of PDHGGs is common and often fatal, and by understanding the role senescent cells play in tumour relapse, novel approaches to treatment can be developed.
Using experimental models and molecular data from tumour cells, the researchers in this project aim to reveal the factors that make cells become senescent. By filling this knowledge gap, scientists can identify new drugs and treatment methods, and also improve the effectiveness of current therapies.
Why is it important?
The survival rate of patients with PDHGGs is extremely low. Treatment options are limited as standard cancer treatments, such as radiotherapy and chemotherapy, have so far been unable to help children diagnosed with brain tumours of this type. If researchers are able to gain further understanding of the role of senescent cells in tumour development and relapse, it could change the way in which treatment for PHDGGs is approached and ultimately improve the outcome for patients.
PDHGGs are devastating tumours with a very low survival rate, for which all tested treatments have so far failed. We will test whether killing senescent cells improves the effect of radiotherapy. These results could support the development of clinical trials by the applicants.
– Prof. Juan Pedro Martinez-Barbera
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Professor Juan Pedro Martinez-Barbera is the Head of the Developmental Biology and Cancer Research & Teaching Programme at Great Ormond Street ICH. He has a background of research in paediatric craniopharyngioma and senolytics, and more recently has been investigating senescence in other types of paediatric brain tumours.
