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The Evolution of Childhood Brain Cancer

The Evolution of Childhood Brain Cancer

Researcher name: Dr Roel Verhaak
Institution: The Jackson Laboratory, U.S.
Grant name: More Data Grant
Grant amount: Up to $672K
Grant years: 2020-2021

Meet the Researcher

Dr Roel Verhaak is a world-class brain cancer researcher. He trained, in part, at the prestigious Broad Institute of Harvard and MIT Institutes in Cambridge (U.S.) and the Dana-Farber Cancer Institute in Boston (U.S.). His research contributed to the definition of clinical categories of brain cancer that are now used by the World Health Organisation.

Experimental models have been extremely useful for learning about cancer and how we might treat it. For brain cancer, however, these models have failed to provide sufficient insight for a breakthrough. This project will use data to help understand what drives brain cancer from models of naturally occurring brain cancer that have never before been explored.

This work could be the beginning of a significant new frontier in brain cancer treatment for children. Striving to treat and cure dogs with cancer, learning what works best and importantly why it works, can inform our own therapy regimens. This provides an important opportunity to improve a child’s brain cancer outcome.

Targeting regions of converging synteny and loss of heterozygosity in paediatric and canine glioma

Brain cancers such as glioma occur in dogs at rates comparable to humans, with short-snouted breeds such as boxers being more susceptible than others. In helping to treat dogs diagnosed with brain cancer, the research team compared the molecular and cellular characteristics of glioma in dogs to their human counterparts and found extensive similarity in particular to aggressive glioma observed in children.

In this project, the team will leverage the similarities between glioma in dogs and in children to further sharpen the lens as to what is causing these cancers. They will mine large datasets on dog and children’s gliomas to precisely define the hundreds of molecular abnormalities found in both disease types. The team will perform a large screen and functionally eliminate each molecular abnormality one by one and evaluate the effects of this depletion on cancer-associated features such as cell growth in human and canine cell models of glioma. This advanced screen is enabled by the versatile and cutting-edge imaging platform and computational expertise at the Jackson Laboratory.

The team expects to see convergence of the most impactful molecular abnormalities on brain cancer’s evolutionary mechanisms, which will implicate that these mechanisms are candidates for the development of new treatments.

Harnessing the Power from Within to Tackle DIPG/DMG

Harnessing the Power from Within to Tackle DIPG/DMG

Researcher name: Dr Matt Dun
Institution: University of Newcastle, AUS
Grant name: Alegra’s Army Grant
Grant amount: Up to $326K
Grant years: 2020-2022

Meet the Researcher

Dr Matt Dun is an exceptional cancer researcher. He has enjoyed continuous Fellowship funding from the Cancer Institute NSW, and the National Health and Medical Research Council since the completion of his PhD (2012); collecting 15 national and international research awards. He added childhood brain cancer research to his program after the devastating diagnosis of his own 2-year-old daughter Josephine, with diffuse midline glioma (DMG), formally known as DIPG.

This project looks to utilise the patient’s own immune system; to harness the power from within and identify signposts on DMG cancer cells that can be used as beacons for the immune system to recognise and subsequently attack the cancer.

The current survival of a child diagnosed with DMG is only 9 months. Through the team’s research efforts, they were able to extend survival for Josie to 21 months, which is an enormous feat despite her tragic passing. The project is now looking at how this was possible and trying to apply these learnings to other children with DMG.

The goal of this project is to increase survival with better immune-based therapies for the treatment of DMG. This was achieved in one case of DMG and the project looks to expand this to other children with DMG.   

Harnessing the power from within: Neoantigen immunopeptidomics for the development of immunotherapies for the treatment of diffuse intrinsic pontine glioma (DIPG)

Occurring in the brain stem, diffuse midline glioma (DMG) is  responsible for half of all brain cancer deaths in children. The brain stem controls vital functions such as breathing and heart rate, plus the nerves and muscles required for sight, hearing, movement, swallowing and speech. Primarily affecting children and young adolescents (median age 7 years), the average survival is just 9 months post diagnosis. Radiotherapy (offered at diagnosis) provides transient benefits and is considered palliative. Tumour location precludes resection and chemotherapy approaches (historical and current) have not increased survival.

Progress in treating DMG faces two major barriers: the lack of DMG-specific biological knowledge, and how to circumvent the brain’s protective mechanism, the blood brain barrier (BBB). The BBB acts as a shield to stop toxins moving from the blood stream into the brain, including chemotherapies and other pharmacological treatments.

Recently, recurring gene mutations that drive DMG disease initiation and progression have been identified. The unique combinations of mutations identified suggest the tumour is able to continue to grow and survive despite specific, mutation-matched, pharmacological targeting. Therefore, to improve outcomes for children with DMG, we look to utilise the patient’s own immune system. To harness the power from within in the fight against DMG. We will identify molecules presented to the patient’s immune system as foreign (i.e. tumour-specific gene products) that can be used in the development of novel immunological therapies.

Biobanking 3.0!

Biobanking 3.0!

Researcher name: Charlie Teo Foundation
Institution: Charlie Teo Foundation, AUS
Grant name: More Data Grant
Grant amount: $340K
Grant years: 2019 →

Dr Charlie Teo has dedicated his time to collecting samples for over 10 years making this resource one of the largest and most varied to study brain cancer. Now in an Australian-first, the Charlie Teo Foundation Brain Tumour Bank will extract DNA from samples and analyse and map their genetic code making this data available for researchers to use. That data essentially creates a virtual copy of the sample, meaning a single sample can now be used in multiple brain cancer studies at the same time!

Charlie Teo Foundation Brain Tumour Bank will take precision medicine – the knowledge of an individual’s genetic code – to the next level. This will form the foundation for researchers to begin to understand how an individuals’ genetic code interacts and behaves with various factors that results in their brain cancer. Understanding this may lead to targeted treatments that will make a significant difference to an individual beating brain cancer.

Charlie Teo Foundation Brain Tumour Bank

Charlie Teo Foundation Brain Tumour Bank is a safe house for samples of human tissue, live cells, DNA and blood to be used for brain cancer research. It will help researchers understand what is unique and different about each individual’s brain cancer and contribute to expanding knowledge on diagnosis, prognosis and treatment.

The Brain Tumour Bank is unique because not only will it collect tissue and blood samples, as routinely collected by Australian brain biobanks, but will determine the precise sequence of every nitrogenous base pair that makes up the genetic code of the patients who have donated their samples. This provides a highly comprehensive, cost-effective, time-saving and invaluable resource for researchers to use to help advance our research of brain cancer.

Charlie Teo Foundation Brain Tumour Bank will also be unique in establishing a cell line repository of real-world brain tumours, which could be utilised in future to learn more about the behaviours of these tumours. Successful development of these cell lines will provide valuable and accurate models that will enable more refined analysis of the mechanisms that regulate individual patient response to treatment and allow the development of models for precision medicine.

Cancer Genomics – The Next Level

Cancer Genomics – The Next Level

Researcher name: Dr Mike Sughrue & A/Prof Joseph Powell
Institution: Garvan Institute of Medical research, AUS
Grant name: More Data Grant
Grant amount: Up to $1.2M
Grant years: 2019 →

Meet the Researchers

Dr Mike Sughrue is a genius. He graduated at the top of his medical school class at Columbia University in New York. He then went on to establish one of the busiest brain tumour centres in the U.S. Mike has even taught himself 10 different languages!

A/Prof Joseph Powell is a pioneer and entrepreneur. He leads an international team of top scientists to study our genetic code and how it causes disease. He’s also developed cutting-edge technologies that can diagnose lung disease in patients non-invasively. 

Cancer Genomics – The Next Level is a world-first large scale study that will organise the billion million bytes of genetic data from Australian brain cancer patients and make it universally accessible and useful. This project is also a prime example of how we’re working to break down silos, bringing together experts in genetics and data to tackle brain cancer.    

This work could change how we currently diagnose and treat brain cancer. Targeted therapies are powerful, but brain cancer is a target with many bullseyes that shift position whenever struck. Understanding how tumours become seething masses of varied cells, all with their own unique mutations will allow us to continue to strike the deadliest parts of the tumour until we hit the bullseye.

A world-first, large scale study of GBM brain tumours to identify intra-tumoural cellular heterogeneity using the single cell sequencing technique

Over the last century, insufficient progress has been made in the management of brain cancer, therefore, a better understanding of its underlying biology is needed. Glioblastomas, the deadliest form of brain cancer, are intricate ecosystems composed of diverse malignant cells and non-malignant cells, whose behaviour as a whole determines response to therapies and patient outcome.

While it is critical to precisely measure all cellular elements in brain cancers, standard genomic and transcriptomic methods profile these complex entities as bulk samples, measuring only the average signal and masking the inherent cellular diversity. Bulk transcriptomic expression profiles have been instrumental in our initial understanding of brain biology and cancer but provide limited insight into tumour differences and identification of rare cellular subtypes that may be the cause of the cancer.

Single-cell analysis techniques (scRNA-seq) provide an opportunity to access information about cellular biology at unprecedented resolution. This advanced technique allows us to analyse the transcriptome from individual cells. scRNA-seq has revealed complex tumour differences and expanded our understanding of cancer initiating cells and tumour microenvironment interactions. A better understanding of the molecular features of brain tumours through scRNA-seq will aid in the development of novel treatment strategies.

The Immune System Strikes Back – Targeting the Kynurenine Pathway

The Immune System Strikes Back – Targeting the Kynurenine Pathway

Researcher name: Dr Seray Adams
Institution: Macquarie University, AUS
Grant name: More Data Grant
Grant amount: $141K
Grant years: 2018-2020

Meet the Researcher

Dr Seray Adams is an up and comer cancer researcher. Driven by her passion to help brain cancer patients, she has learned from Australia’s leading brain cancer researchers and now leads innovative brain cancer research.

The Kynurenine Pathway has long been implicated in helping cancer cells evade the immune system. However, this project questions the accepted by looking at the lower segment of this pathway, which is not currently focused on and investigates ways to switch it back in favour of attacking the cancer, instead of protecting it.

Immunotherapies, the clinical regimens that empower a patient’s immune system to fight the disease like it might fight an infection, has been successful in many cancers but failed in brain cancer. If we can find an immunotherapy to work in brain cancer, no other drug or course of treatment can generate the long-term benefits of having our immune system keeping constant surveillance for any future cancer growth.   

Investigating the kynurenine pathway as a potential biomarker for predicting glioma patient prognosis and tumour grade

Activity of a metabolic pathway in cancer prevents the immune system from maintaining control over cancer growth. One metabolic pathway known to help the cancer avoid destruction from the immune system is tryptophan metabolism. This research aims to understand how this pathway disrupts the immune system and contributes to brain cancer aggressiveness. Understanding the role the pathway plays in promoting brain cancer growth could identify new treatment strategies for treating brain cancers. Utilising the pathway as a clinically useful tool may allow more accurate brain cancer diagnosis and better predict patient survival and tumour aggressiveness.