Weifan Dong, University of Toronto
Scientific publication
Weifan Dong, Adam Fekete, Xiaodi Chen, Hongwei Liu, Greg L. Beilhartz, Xin Chen, Shahrzad Bahrampour, Yi Xiong, Qi Yang, Hongyu Zhao, Tian Kong, Malia S. Morioka, Geena Jung, Ji-Eun Kim, Daniel Schramek, Peter B. Dirks, Yuanquan Song, Tae-Hee Kim, Ye He, Siyi Wanggou, Xuejun Li, Roman A. Melnyk, Lu-Yang Wang & Xi Huang. A designer peptide against the EAG2–Kvβ2 potassium channel targets the interaction of cancer cells and neurons to treat glioblastoma. Nature Cancer 4, 1418–1436 (2023). https://doi.org/10.1038/s43018-023-00626-8
Identification of a potential new treatment for glioblastoma
Glioblastoma is an extremely lethal brain tumor, with an almost 100% fatality rate. A single chemotherapy drug as part of the standard-of-care exists to treat patients, but it has limited efficiency. A new publication by Weifan Dong and colleagues report several significant discoveries that could have life-changing consequences for patients with glioblastoma.
The researchers first identified two potassium channel proteins, named EAG2 and Kvβ2, that form a glioblastoma-specific protein complex. This complex facilitates the growth and invasion of glioblastoma. They then unraveled the mechanism responsible for the formation of the EAG2–Kvβ2 complex. This process requires a specific form of the Kvβ2 protein that is exclusively expressed in glioblastoma.
With this knowledge, the researcher developed a small peptide therapy designed to block the formation of the EAG2–Kvβ2 complex. This peptide therapy significantly suppressed glioblastoma growth and extended the survival of preclinical glioblastoma mouse models. Furthermore, they elucidated the mechanism of action of this peptide and demonstrated its robust efficacy in treating glioblastoma that is resistant to conventional chemotherapy.
These exciting findings have the potential to pave the way for the development of the next-generation therapeutic agent, offering hope for patients with glioblastoma, a lethal disease that causes unbearable consequences to the afflicted patients and their families.
This publication has gathered significant interest from the scientific community and public media. In addition, the intellectual property of this paper, centered around the design and application of the peptide therapy for treating glioblastoma, has been patented (U.S. Patent No. WO/2023/065046). This achievement underscores the innovative nature of this research. The research team, led by Dr. Xi Huang, is working with Office of Industry Partnerships & Commercialization at The Hospital for Sick Children to move this discovery towards clinical trials, with the ultimate goal of benefiting patients grappling with glioblastoma.
About Weifan Dong
This project commenced in 2015 when Weifan Dong joined the lab of Dr. Xi Huang at The Hospital for Sick Children and University of Toronto as a graduate student. Weifan Dong not only conducted the majority of the experiments detailed in this paper but also contributed to the conceptualization of experiments and the research direction. Notably, he took a leading role in elucidating the mechanism behind the formation of the protein complex and in the design of the peptide therapy. Furthermore, Weifan Dong built connections with multiple collaborators both locally and globally. His substantial contributions throughout this research are undeniably significant.
Sources of funding
This work was supported by Canadian Cancer Society, SickKids Foundation, Arthur and Sonia Labatt Brain Tumour Research Centre, Garron Family Cancer Centre, Conquer Cancer Foundation, b.r.a.i.n.child, Sontag Foundation, Meagan’s HUG, Natural Sciences and Engineering Research Council, Ontario Institute for Cancer Research, Canadian Institute of Health, and Canada Research Chair program.
