Glioma is a potentially fatal neurological disorder with limited interventional treatment, despite extensive research over the past several decades. A research team led by Dr. Jung Chen, a former professor at Pennsylvania State University who now leads the Center for Brain Repair at Jinan University in China, has developed a novel gene therapy to reprogram glioma cells into functional neurons, shedding new light on treating glioma. . The work was published on Cancer Biology and Medicine On March 22nd, 2021
Glioma is a common malignant cancer that grows in the central nervous system. For patients with a type of acute glioma called glioblastoma, the average survival time is usually less than 15 months. Surgical removal followed by chemotherapy and / or radiotherapy is one of the main methods of treatment but has limited effectiveness. Several clinical trials are underway using immune cells engineered to target primary or recurrent glioma, but they still face serious hurdles to resolve.
Glioma results from aggressive proliferation of glial cells. Chen’s team previously published a series of work showing that endogenous glial cells in the brain can be converted directly into functional neurons after overexpression of neurotransmitter factors such as NeuroD1 and Dlx2. In this work, the team expanded their research from glial cells to glioma cells and discovered that neurotransmission factors can also efficiently convert glioma cells into neurons.
Professor Chen commented: “Our cell-shifting therapy for glioma is completely unique and distinct from conventional cancer treatments that usually aim to kill cancer cells.” One of the main side effects of killing cancer cells is the inevitable collateral damage to normal cells. On the other hand, when we use gene therapy technology to convert glioma cells into nerve cells, the normal cells are slightly affected, “Professor Chen explained why they developed this new technology.
“Another important advantage of our gene therapy approach is that after the overexpression of a neurotransmitter factor (s) such as NeuroD1 or other transcription factors in glioma cells, glioma cells stop proliferating immediately before becoming neurons. This transcription factor-based gene therapy provides a new strategy to lengthen the time window for treatment by stopping the rapid spread of malignant glioma cells, ”added Dr. Chen Wang, first author of this work.
While Professor Chen and colleagues were excited about their new findings, they also acknowledged that this new technique for treating glioma with transcription factor-based gene therapy is still in infancy. Several technical issues have yet to be considered, such as developing a safe viral delivery system, targeting glioma cells in a specific manner, and potential side effects caused by neurotransmitter factors. They also plan to combine cell diversion therapy with other interventions to achieve synergistic effects for treating glioma.
In addition to Professor Chen and Dr. Wang, other contributors to this work include Dr. Zivi Bai, Asma Hussain, and Yuting Bay from Pennsylvania. This work was supported by the Charles H. “Skip” Smith Endowment Fund of Professor Chen.