DIPG/DMG Research Projects supported by RUN DIPG
Currently, there are no recognised treatment options for DIPG – a fact that is truly heartbreaking. To ensure we move towards a cure as quickly and effectively as possible, RUN DIPG supports research in areas that show promise, including the following:
- Treatment & therapies
- Essential technology
- Bright minds
Connecting the dots with Combination Analysis
RUN DIPG are immensely proud to support a three-year research project in conjunction with The Kids’ Cancer Project and The University of Newcastle (UON). Led by Associate Professor Matt Dun, the Cancer Signalling Research Group (CSRG) are particularly interested in the interplay between the genetics of a patient’s tumour and the proteins that control the wayward growth and survival processes that are the hallmark of DIPG/DMG malignancy.
The project involves moving the findings of another RUN DIPG-funded research project to a more patient-specific study. Nicknamed “PHOTON” (PHarmaco-phOspho-proTeO-geNomics), Matt and the team will utilise donated tumour tissue to reveal the tumour’s genetics (the genome), the proteins (the proteome) and the protein activity (the phosphoproteome), which combine to control tumour growth.
Concurrently, the lab will develop a set of patient-specific tumour models to test therapies that act on targets identified within the “-omic” data sets. Initially, a ‘cell line’ will be cultured from a small portion of the tumour sample by supplying nutrient media and incubating at conditions optimised for cancer cell growth. The therapies showing the greatest effect at reducing or stalling the growth of the tumour cell line will be progressed to a patient-matched animal study to further assess safety, tolerability and effectiveness.
Importantly, Matt and the team will simultaneously study the effect of therapies identified by both genomic and phospho-/proteomic approaches throughout the project. Presently, children and families diagnosed with DIPG/DMG are offered palliative radiation therapy in an attempt to shrink the tumour and reduce symptoms. Subsequently, experimental therapies may be offered or sought via enrolment in clinical trials or direct from pharmaceutical companies if compassionate access schemes are available. Historically, these investigational therapies act on genomic characteristics that have been identified within the patient’s tumour. As we know all too well, this approach is yet to find a treatment that extends DIPG/DMG patient survival.
Over three years, A/Prof Dun and PhD Candidate Izac Findlay will collate the findings for each tumour analysed to see whether a pattern can be identified relating the underlying genetic or protein-specific characteristics of a tumour to the effective therapies identified and tested via the PHOTON platform. It is hoped that this approach can be developed to facilitate immediate treatment selection for patients at diagnosis, enabling improved survival without having to face the current “gamble” of experimental therapies on offer.
As well as the commitment of The Kids Cancer Project and the institutional support provided by The University of Newcastle, we must thank you, the RUN DIPG runner, mover, supporter, follower or donor – without our dedicated community; our charity could not be in a position to be able to bring this promising work to fruition. Thank you, thank you, thank you!
Investigating combination therapies on an international scale
Developed thanks to RUN DIPG-funded research
As confronting as a DIPG/DMG diagnosis is, the realisation that there are no recognised treatment options for the condition is truly heartbreaking. Upon diagnosis, families are given the option to undergo radiation therapy (RT) in an attempt to shrink the tumour and reduce symptoms of the disease.
Following a DIPG/DMG diagnosis, families often begin a desperate search for experimental options that may help give their child ‘more time’. This may be in the form of a clinical trial and requires patients meet certain criteria if they are to be eligible to receive the drug being studied. Eligibility criteria exist so that researchers can be sure that any benefit (or harm) observed in the trial can be attributed to the medicine being studied and not individual circumstance (as best as possible).
For many families, finding a clinical trial that their child qualifies for means they must travel overseas, a significant financial, logistical and emotional process. It is for this reason, that one of RUN DIPG’s major goals is to support the opening of ‘Combination Therapy for the Treatment of Diffuse Midline Gliomas’ (nicknamed “DMG-ACT”)– an international, adaptive clinical trial studying combination therapies against DIPG/DMG, with the flexibility of adding or switching the drug of interest based on the latest findings of the field.
Notably, A/Prof Dun and the Cancer Signalling Research Group have contributed to much of the groundwork in the development of the DMG-ACT trial protocol. Two drugs to be studied include paxalisib and ONC201, a combination that Josie Dun was the first child to receive worldwide, thanks to the pre-clinical studies Matt and the team worked hard to complete following Josie’s diagnosis.
With 23 collaborating sites expected to participate worldwide, we cannot wait to see DMG-ACT open for local enrolments. Matt and the University of Newcastle team are working with the Australian and New Zealand Children’s Oncology and Haematology Group (ANZCHOG) responsible for coordinating national trials such as these in Australia.
We at RUN DIPG are committed to facilitating the process; it will be thanks to our supporters that Australian families facing DIPG/DMG finally have accessible treatment options, fully back by rigorous scientific method and without the need for international travel.
Currently enrolling in the United States, you can read more about the clinical trial via the Pacific Pediatric Neuro-Oncology Consortium’s website .
Backing Brains to beat brain cancer
In Izac’s own words…
‘…Genetic mutations alter the activity of the normally, very-well-controlled proteins that regulate cell growth and survival, resulting in cancer. For children diagnosed with pHGG, we are yet to fully understand how these dysregulated proteins function. As proteins are often the target of candidate drug therapy, this is a significant knowledge gap if we are aiming to bring about better survival for pHGG (paediatric high-grade glioma, such as DIPG/DMG) patients.
My project seeks to develop a holistic evidence-based analysis platform that will characterise each tumour’s genome (the sum of genetic alterations) and proteome (complete set of proteins expressed by the tumour), with the goal of understanding which protein-targeting therapy may be most effective for a tumour with a particular genetic signature.
My hypothesis is that by coupling genomic and proteomic analysis, drug screening and patient-derived tumour models, we will characterise the network of protein-controlled signalling pathways that drive the relentless growth/survival of each individual’s tumour. I will utilise this information to design or reposition combination treatment approaches that address the wayward activity of cancer-sustaining proteins, with the ultimate goal of providing individualised, targeted treatment options for pHGG patients and their families…’
Izac we wish you the very best throughout the coming years’ studies, we’re excited to see what this specialized approach will bring for DIPG/DMG patients, clinicians and the research field.
DIPG/DMG Research support Hudson Institute of Medical Research
RUN DIPG are proud to support the work of Dr Jason Cain at the Hudson Institute, Clayton Victoria.
Also a member of the DMG-ACT Pre-clinical Working Group (supporting the latest DMG clinical trial), RUN DIPG has awarded Dr Cain a $64,191.70 contribution to support his team identify new therapies for DIPG. Focused on understanding the mechanisms that drive DIPG/DMG development and progression, we are proud to support critical research needed to improve DIPG survival.
Investigating promising anti-DIPG therapy ONC201
A/Prof Matt Dun examines promising anti-DIPG therapy ‘ONC201’ and the lengths parents are forced to go to source supply
In one of our most meaningful research announcements we have had the pleasure of making, we are proud to highlight the publication of the scientific journal article, “Preclinical and clinical evaluation of German-sourced ONC201 for the treatment of H3K27M-mutant diffuse intrinsic pontine glioma” in Neuro-Oncology Advances.
A collaboration between the Dun Lab at the University of Newcastle, Hunter Medical Research Institute and the Chemistry Department at UNSW, the report collates the clinical journey of 28 children and their families who sourced anti-DIPG drug ‘ONC201’ from Germany. One of the main findings was that the German version of ONC201 showed the same preclinical and clinical efficacy as the compound used in clinical trials in the USA.
Whilst the findings provide hope and reassurance to DIPG and DMG families that may take this path, we acknowledge the families and the children for whom German-sourced ONC201 provided short-lived or no benefit.
With the excellent brainstem accessibility of ONC201 highlighted in this study, coupled with the emerging mechanisms of action revealed by Dun Lab, we can’t wait to see if DIPG research can finally bring us a combination drug strategy that delivers long-term DIPG/DMG survivorship.
radiation therapy modelling capabilities at University of Newcastle
Thanks to the hard work and commitment of our supporters, we are thrilled to be able to provide equipment funding to the Dun Lab at The University of Newcastle, Australia. Associate Professor Matt Dun, Dr Ryan Duchatel and the Newcastle team will be able to ‘level-up’ their DIPG/DMG research with the purchase of a Cabinet X-ray Irradiator ($281,075).
The acquisition will allow the Dun Lab to study the effect of radiation therapy (RT) on DIPG/DMG tumours, including how to improve response to RT – very important seeing as all DIPG/DMG patients are offered RT in an attempt to shrink the tumour and reduce symptom burden!
Crucially, this equipment will provide A/Prof Dun and the team a more ‘true-to-life’ model of how DIPG/DMG tumours respond to the experimental drugs or immune-based therapies they are studying in their laboratory. They will now be able to pre-treat DIPG cells/tumours with RT before applying a drug of interest – just as would happen for DIPG patients in the clinic.
support at The Children’s National Hospital Washington
Thanks to the ongoing commitment of our RUN DIPG community, we are once again humbled to announce our funding of much-needed DIPG/DMG research.
Aiming to understand and enhance the effect of two promising anti-DIPG therapies, RUN DIPG are proud to support the work of Professor Javad Nazarian, at the Children’s National Hospital, Washington D.C, with an $80,000 commitment.
Oral therapies ONC201 and paxalisib (that will be studied in the international clinical trial ‘Combination Therapy for the Treatment of Diffuse Midline Gliomas’) will be the focus of Dr Nazarian’s work. His team will look to find ways to improve the rate and duration of response to these two drugs (having previously been deemed safe for paediatric patients) by testing unique triple drug therapy approaches.
This work is an extension of past collaborative projects between Prof Nazarian and Associate Professor Matt Dun at the University of Newcastle, Hunter Medical Research Institute. Considered a field leader in DIPG/DMG research, we are looking forward to the insights A/Prof Nazarian and his team’s work will provide, so that more children may receive robust benefit from ONC201 and paxalisib therapies in their fight against diffuse midline glioma.
As always, these important projects cannot happen without the support and dedication of our runners, movers, followers and advocates – Team RUN DIPG, keep doing what you’re doing, together we will make the difference.
The Dun Lab ‘research round-up’
Cold brains warm researchers’ hearts
The capacity of A/Prof Dun and the Cancer Signalling Research Group at the University of Newcastle has greatly expanded this week thanks to RUN DIPG’s recent grant of $63,191 for the purchase of freezer equipment.
Required to store precious DIPG/DMG tumour samples and frozen immortalized cell lines developed by the group, the ultra-low temperature equipment was a welcome update for the space. Like a kid with the latest new toy, Postdoctoral Researcher Dr Ryan Duchatel was keen to get the units powered up, reduced to temperature and put to use ASAP when he guided the install in February.
“…we’re always grateful for the support RUN DIPG provides our work and of the hard work their donors and supporters have put in to raise the funding. We’re looking forward to making everyone proud via some great research outcomes in the near future, we can’t wait to get into it!”
Introducing Ms Mika Persson
RUN DIPG International HDR Scholarship Recipient, 2020
The ‘RUN DIPG International PhD Scholarship’ commenced in the later months of 2020 and progressed through 2021 despite the unexpected ‘offshore’ setting. Committing approximately $108,000, RUN DIPG’s funding supports the project titled ‘Neoantigen immunopeptidomics for the development of immunotherapies for the treatment of diffuse intrinsic pontine glioma (DIPG)’.
Scholarship recipient Ms Mika Persson has a Bachelor of Biomedicine from Karolinska Institute, Sweden. Whilst unable to enter Australia, Mika was able to refine her skills in quantitative mass spectrometry from Matt’s own mentor- Prof Martin Larsen at The University of Southern Denmark.
Arriving in Newcastle in November 2021, Mika, Matt and the Cancer Signalling Research Group are excited to both learn from Mika as she shares the techniques she has developed in the past months and to have her finally join the Dun Lab in person.
Mika has commenced the process of identifying unique structures present on the surface of DIPG cells, called ‘neoantigens’. Knowledge about these neoantigens can then be used to develop an immune-based therapy targeting the tumour (not healthy tissue). This approach has had much success in other types of cancer, particularly melanoma and some blood leukaemias.
Mika we are proud to support the important project you will undertake throughout your post-graduate studies, and we look forward to hearing about your progress in our 2022 report!
DIPG Research at the University of Newcastle Funded by RUN DIPG
The determination of A/Prof Dun and the Cancer Signalling Research Group (CSRG) did not wane throughout 2020/21 even though many research teams around the world were forced to ‘hit pause’ thanks to COVID-19. RUN DIPG were proud to support this important work throughout such an uncertain time.
Granting more than $176,000 in research funding, A/Prof Dun continued to lead the Cancer Signalling Research Group (CSRG) in an effort to improve the field’s understanding of the underlying mechanisms controlling the growth of DIPG tumours, as well as finding/developing therapies to combat the devastating course of the disease.
The crux of this project is that knowledge of either the proteome, or the genome alone, does not ensure a complete understanding of a tumour’s likelihood to respond to, or resist a particular therapy, hence, RUN DIPG have been delighted to be able to keep this important work moving in 2020 and 2021 thanks to our supporters.
Future Research Commitments
RUN DIPG are committed to continuing our support of DIPG/DMG research with the following in our sights as the next areas of investment:
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