Cure Brain Cancer Foundation’s 2017 Contribution to the DIPG Collaborative

Project title Cure Brain Cancer Foundation’s 2017 Contribution to the DIPG Collaborative
Grant Amount
$31,878
Institution
Several
Investigator Team
Several
Grant Type
Collaborative Grant
Years
2017 – 2018

The DIPG Collaborative is made up of over 20 foundations cooperatively funding $1-2 million to DIPG research every two years. Cure Brain Cancer Foundation is a proud Foundational Partner of the Collaborative and allocated $31,878 to the Collaborative in 2017. In 2017, the DIPG Collaborative awarded $1.97 million to 17 world-class research projects.

  • Grant 1: Targeting neuronal activity regulated DIPG infiltration (Dr. Michelle Monje, Stanford University, $200,000)

  • Grant 2: Targeting DIPG through pharmacological activation of mitochondrial biogenesis: an in vitro and in vivo preclinical study (Dr. Cynthia Hawkins, The Hospital for Sick Children, $162,828)

  • Grant 3: Developing novel combination therapeutic approaches for DIPG targeting Polo-like kinase 1 (Dr. Laura Franshaw, Children’s Cancer Institute, $185,706)

  • Grant 4: Defining the molecular mechanisms of DIPG development and progression to uncover novel therapeutic targets (Dr. Tak Mak, The Campbell Family Institute for Cancer Research, $100,000)

  • Grant 5: Investigating the role of DIPG-derived exosomes in tumour growth and invasion (Dr. Maria Vinci, Ospedale Pediatrico Bambino Gesu, $98,987)

  • Grant 6: MRI Guided Focussed Ultrasound: Towards clinical translation in DIPG (Dr. Saira Alli, The Hospital for Sick Children, $100,560)

  • Grant 7: Toward a multimodality cure for DIPG: Investigation of intratumoral drug penetration and craniospinal irradiation (Dr. Adam Green, Anschutz Medical Campus, $50,000)

  • Grant 8: Validation of TAK228 as an effective drug for treating children diagnosed with DIPG (Dr. Javad Nazarian, Children’s National Medical Centre, $200,000)

  • Grant 9: Targeting DIPG through combining a super-activator (MCB-613) of steroid receptor coactivators with radiation: an in vivo study in patient-derived intra-brain stem xenograft models (Dr. Xiao-Nan Li, Texas Children’s Hospital and Children’s Hospital of Chicago, $200,000)

  • Grant 10: Elucidating the underlying mechanisms of radioresistance at diagnosis and relapse in DIPG (Dr. David Castel, Goustav Roussy, $101,868)

  • Grant 11: Combination strategies alongside ACVR1 inhibition in DIPG (Dr. Chris Jones, Institute of Cancer Research, $102,432)

  • Grant 12: Low dose mefloquine in mouse models (Dr. Bakhos Tannous, Massachusett General Hospital, $50,000)

  • Grant 13: An open label single arm phase I/II study of MTX110 delivered by convection-enhanced delivery in patients with DIPG previously treated with external beam radiation therapy (Dr. Sabine Mueller, University of California San Francisco, $70,000)

  • Grant 14: Targeting EZH2 as a therapeutic strategy in DIPG (Dr. Richard Phillips, Memorial Sloan Kettering Cancer Centre, $100,000)

  • Grant 15: Determine in efficacy of BMP and MEK inhibitors with radiation to treat ACVR1 mutant DIPG (Dr. Oren Becher, Ann & Robert H. Lurie Children’s Hospital, $100,000)

  • Grant 16: Defining the cellular architecture of DIPG through large-scale single-cell RNA sequencing analyses (Dr. Mariella Filbin, Dana Farber Cancer Institute, $100,000)

  • Grant 17: Advanced RNAi therapeutics for DIPG (Dr. Sena Esteves, University of Massachusetts Medical School, $50,000)

“The DIPG Collaborative is a collection of foundations with the shared mission of efficiently funding and inspiring DIPG cancer research with the belief that through a cure for DIPG, significant advances in other cancer research will be made.”

Mission of the DIPG Collaborative

Progress

Cure Brain Cancer Foundation funds to the DIPG Collaborative were allocated to Dr. Laura Franshaw’s grant at the Children’s Cancer Institute. Her progress is outlined below; 

Polo-like Kinase 1 (PLK1) is involved in different stages of cell growth and division. It also plays a central role in cell cycle progression. Our research revealed that PLK1 inhibition in DIPG induces cell cycle arrest and apoptosis. Two PLK1 inhibitors, BI2536 and Volasertib proved to increase survival in preclinical models of DIPG. We also tested combination therapies to be used with PLK1 inhibitors, including temsirolimus and panobinostat. Further preclinical models demonstrated that PLK1 blockade enhances the therapeutic effects of radiation in DIPG. 

Dual targeting of the epigenetic pathway and the radiosensitising properties of PLK1 inhibitors provide promising prospects for combination therapies against DIPG. Further assessment of PLK1 combinations with HDACi, RTKi and radiation warrant further investigation.