A UOW research team spanning across synthetic chemistry and neurobiology in the School of Chemistry and Molecular Bioscience have been working on a new glioblastoma treatment since 2014. A recent paper (2018) in the Journal of Neurochemistry, is the first published evidence of how well the drug works against glioblastoma cells (in vitro) while leaving healthy cells unscathed.
The promising preliminary research into the drug aims to overcome the lack of treatments for this very aggressive brain tumour that proliferates and migrates rapidly, leaving patients with a life expectancy of only 12-15 months.
The team has engineered a dual action or two-pronged attack drug which is activated by the high hydrogen peroxide levels typically found near glioblastoma cells in the brain. Once activated, the drug releases a gene expression regulator along with a glutathione scavenger to amplify cell stress pathways and ultimately kill glioblastoma cells without affecting healthy neighbouring cells.
This video depicts the dual action or two-pronged attack drug which is activated by the high hydrogen peroxide levels typically found near glioblastoma cells in the brain. Once activated, the drug releases a gene expression regulator along with a glutathione scavenger to amplify cell stress pathways and ultimately kill glioblastoma cells without affecting healthy neighbouring cells.
In 2012 a chance meeting between the two leaders of the project, Dr Chris Hyland and A/Prof Lezanne Ooi at a book shop led to the development of the ideas behind the drug for glioblastoma. A/Prof Lezanne Ooi has been working with gene expression regulator drugs for over 16 years, while Dr Chris Hyland’s lab has been developing new ways to synthesise the types of molecule found in the new drug for over 10 years. Combining the gene expression regulator with the glutathione scavenger was part of the PhD research of Dr Yi Sing Gee, a synthetic and medicinal chemist in Dr Chris Hyland’s laboratory.
“It was an exciting opportunity to use our knowledge of chemical reactivity to design a new dual action anti-cancer drug that would selectively release the reactive components of the drug only in cancerous cells, not healthy ones.” Says Dr Chris Hyland
The double hit strategy is a game changer in the team’s drug development strategy against cancer, with future work assessing the drug’s effectiveness in vivo.
A further publication is being planned to report on the work on the gene expression inhibitors which formed the experimental foundation for this project.
“We were very impressed to see how well this drug behaved in vitro against different types of glioblastoma and across a range of important criteria, while remaining selective for cancerous cells”, says Dr Engel a research fellow in A/Prof Lezanne Ooi’s lab who conducted the in-vitro studies.
The research was partially funded by a previous NHMRC Project Grant as well as a UOW-ANSTO Joint Seed Grant.
The research team at UOW pictured below is (from left-right): Dr Martin Engel, Dr Yi Sing Gee, A/Prof. Lezanne Ooi and Dr Chris Hyland
- THE PUBLICATION WITH A FULL LIST OF AUTHORS AND INSTITUTIONS IS AVAILABLE AT:
Authors: Martin Engel, Yi Sing Gee, Dale Cross, Alan Maccarone, Benjamin Heng, Amy Hulme, Grady Smith, Gilles J. Guillemin, Brett W. Stringer, Christopher J. T. Hyland, Lezanne Ooi
Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia
School of Chemistry and Molecular Biosciences, University of Wollongong
Mass Spectrometry User Resource and Research Facility, School of Chemistry, University of Wollongong
Faculty of Medicine and Health Sciences, Macquarie University
QIMR Berghofer Medical Research Institute, Queensland