Abstract
AB001. Development of tumour-targeted therapy for the treatment of adult and paediatric high-grade gliomas
Jiney Jose1, Peter J. Choi1, Thomas I. H. Park2, Carine Lee2, Michael Dragunow2, Chae-Yong Kim3, Elizabeth Cooper2, Kihwan Hwang3, Kyung M. Nam3, William Denny1
1Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Auckland, New Zealand;
2Department of Pharmacology, University of Auckland, Auckland, New Zealand;
3Department of Neurosurgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si, South Korea
Correspondence to: Jiney Jose, PhD. Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Grafton, Auckland 1023, New Zealand. Email: j.jose@auckland.ac.nz.
Background: Brain cancer patients, especially those suffering from high-grade gliomas (HGGs) face a bleak future with very dismal long-term disease-free survival outcomes due to the limited treatment options currently available. Therefore, there is an unmet need for new therapeutic intervention that extends patients’ progress-free survival and improves their quality of life. A significant hurdle is the inability of current chemotherapy agents to cross the blood-brain barrier (BBB). BBB acts as a protective shield that filters the blood to ensure nothing harmful makes it to the brain. This protection is usually good, but it becomes a problem if you want to deliver therapeutic cancer drugs through it. This barrier blocks 98% of drugs from entering the brain. Even the ones that cross BBB are unevenly distributed in the normal brain and tumour tissue, resulting in mediocre treatment and severe side effects.
Methods: We are developing drug delivery systems that can cross the BBB and facilitate the specific accumulation of drugs in the tumour tissue. This will significantly improve the efficacy of anticancer drugs in treating various brain cancers and reduce systemic toxicity. Our group has explored and developed BBB crossing and tumour targeting near infra-red dyes, which can be covalently attached to Food and Drug Administration (FDA)-approved chemotherapy agents (drug-dye conjugates), thereby delivering it to the tumour tissue.
Results: We synthesized such drug-dye conjugates to target various aberrant pathways in HGG and tested these conjugates against patient-derived HGG cell lines. One such conjugate was tested on a mouse model of glioblastoma, an aggressive form of HGG, and shown to cross the BBB and specifically accumulate in tumour tissue, bringing forth tumour burden reduction.
Conclusions: The results obtained from this work serve as proof of principle that enables tumour-specific drug delivery to treat HGG. This work also paves the way for treating other brain cancers and central nervous system (CNS) disorders like Parkinson’s and Alzheimer’s disease, for which no adequate therapy exists.
Keywords: High-grade glioma (HGG); blood-brain barrier (BBB); tumour-specific drug delivery
Acknowledgments
We thank Associate Professor Kihwan Hwang for his guidance with the animal work reported in the study. We thank Miss Elizabeth Cooper for establishing the initial cellular testing studies for the compouds.
Funding: This study was supported by the Neurological Foundation and Cure Kids.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cco.amegroups.com/article/view/10.21037/cco-24-ab001/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Experiments were performed under a project license (No. 2127 PRG) granted by the national ethics board in compliance with South Korean national or institutional guidelines for the care and use of animals.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the noncommercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
Cite this abstract as: Jose J, Choi PJ, Park TIH, Lee C, Dragunow M, Kim CY, Cooper E, Hwang K, Nam KM, Denny W. AB001. Development of tumour-targeted therapy for the treatment of adult and paediatric high-grade gliomas. Chin Clin Oncol 2024;13(Suppl 1):AB001. doi: 10.21037/cco-24-ab001
