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National brain tumour research funding needs to increase to £30-35 million a year

Meningioma in childhood cancer survivors and medulloblastoma recurrence

Research:

Pooled Analysis of Meningioma Risk Following Treatment for Childhood Cancer Meningioma is the most common abnormal tissue growth following cranial irradiation among survivors of childhood cancer.  Published in Jama Oncology, this study aimed to evaluate the meningioma risk in survivors of childhood cancer following radiotherapy and chemotherapy, and identify possible modifying factors of radiation-associated risk. They concluded that the meninges are highly radiosensitive, especially for children treated before age 10 years. They also found that increasing radiation dose was associated with increased risk of meningioma, and suggested that the persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.

Dormant SOX9-positive cells facilitate MYC-driven recurrence of medulloblastoma Published in Cancer Research, this study investigated recurrence in medulloblastoma. It showed that SOX9-positive cells accumulated in medulloblastoma relapses, and SOX9 was essential for relapse initiation and depended on suppression of MYC activity to promote therapy resistance, epithelial-mesenchymal transition, and immune escape. They suggested that recurrence-specific targeting coupled with DNA repair inhibition comprises a therapeutic strategy in patients affected by medulloblastoma relapse.

Treatments:

Chronic convection-enhanced delivery of topotecan for patients with recurrent glioblastoma: a first-in-patient, single-centre, single-arm, phase 1b trial This study, published in The Lancet Oncology, investigated the safety and effectiveness of chronic convection-enhanced delivery (CED) of topotecan for recurrent glioblastoma.  Topotecan has been shown to be cytotoxic to glioma cells, but is toxic when delivered systemically and has problems traversing the blood brain barrier. 5 patients were fitted with an intercranial implant to deliver the drug directly to the tumour. The authors reported some side effects but, even with those in mind, they reported that CED could be a way to target glioblastomas with drugs that have been previously difficult to deliver.

A sequential targeting strategy interrupts AKT-driven subclone-mediated progression in glioblastoma Published in Clinical Cancer Research, this study aimed to identify and molecularly target tumour cells that can survive, adapt, and subclonally expand under primary therapy. They found drug-resistant ALDH1A1+/pAKT+ subclones accumulate in patient tissues upon adaptation to temozolomide therapy. Their study proposes the combination of temozolomide and AKT inhibitors in a sequential treatment schedule as a rationale for future clinical investigation.

Opportunities:

Children with Cancer UK are welcoming applications for research grant applications. With a funding budget of £2.5 million, individual institutional grants of up to £350,000 are available for research into improvements of the cancer pathway for children and young adult cancers. Example research areas include;

-        Development of novel therapeutic approaches and mitigation of treatment related toxicity

-        Advancement of approaches to diagnosis and identification of markers to monitor disease progression  

The closing date for preliminary applications is Monday 14th November 2022.

Visit: https://cwc.flexigrant.com/ to register and apply under this grant call. For questions related to this grant call, contact the Children with Cancer UK research team at research@childrenwithcancer.org.uk

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