The Olivia Hodson Cancer Fund funded this Research by Stefanie Meier, Sandra Cantilena, Maria Victoria, Niklison Chirou, John Anderson, Darren Hargrave, Paolo Salomoni, Jasper de Boer and David Michod.
Alcohol-abuse drug disulfiram targets pediatric glioma via MLL degradation
Pediatric gliomas comprise a broad range of brain tumors derived from glial cells. While high-grade gliomas are often resistant totherapy and associated with a poor outcome, children with low-grade gliomas face a better prognosis. However, the treatment oflow-grade gliomas is often associated with severe long-term adverse effects. This shows that there is a strong need for improvedtreatment approaches. Here, we highlight the potential for repurposing disulfiram to treat pediatric gliomas. Disulfiram is a drugused to support the treatment of chronic alcoholism and was found to be effective against diverse cancer types in preclinicalstudies. Our results show that disulfiram efficiently kills pediatric glioma cell lines as well as patient-derived glioma stem cells. Wepropose a novel mechanism of action to explain disulfiram’s anti-oncogenic activities by providing evidence that disulfiram inducesthe degradation of the oncoprotein MLL. Our results further reveal that disulfiram treatment and MLL downregulation inducesimilar responses at the level of histone modifications and gene expression, further strengthening that MLL is a key target of thedrug and explaining its anti-oncogenic properties.
The full article is available on nature.com via this link.
Projects
Research into drug repositioning for treatment of rare brain tumours
Acute Myeloid Leukaemia (AML) is a heterogeneous blood cancer that accounts for 15-20% of all paediatric acute leukaemia cases. Despite it's low incidence in children, it is a life-threatening …Identification of novel surface antigen targets for CAR T cell strategies in paediatric Acute Myeloid Leukaemia stem cells
Acute Myeloid Leukaemia (AML) is a heterogeneous blood cancer that accounts for 15-20% of all paediatric acute leukaemia cases. Despite it's low incidence in children, it is a life-threatening …
Reducing Stress and empowering children undergoing operations with the use of Lip balms on breathing masks.
It has been found that by providing children with a choice of flavoured lip balms to put onto their breathing masks before undergoing operations is beneficial in many ways.
Toward drug repurposing in epigenetics: Targeting histone modifications as a novel approach for a selective treatment for DIPG.
Diffuse intrinsic pontine glioma (DIPG) is a very aggressive tumour that mostly affect young children and is the main cause of brain tumour death in children. Mutations that cause …
Identifying the needs of childhood cancer survivors as they approach adulthood
An OHCF-funded study will help healthcare professionals at GOSH understand the ongoing needs of children who have survived cancer, thereby improving the care they receive as they enter adolescence.
Characterising novel therapeutic targets for neuroblastoma
OHCF is supporting significant research into potential new therapies for this very serious form of childhood cancer.
Delivering rapid and efficient genetic screening for bone marrow failure syndromes
A new, more efficient method of DNA sequencing will help ICH scientists quickly identify causes of bone marrow failure syndromes.
Understanding more about relapse in young patients with acute lymphoblastic leukaemia
Funds donated by OHCF will enable haematologists at GOSH use a form of DNA sequencing to help them treat and prevent relapse of a common childhood cancer.
Evaluating expanded tumour infiltrating lymphocytes (TILs) in children’s solid cancers
A pilot study by the Institute for Child Health aims to understand how a treatment that has generated a response in some adult cancer patients might also have a …