Current understanding of gliomagenesis: from model to mechanism
Juanjuan Luo1,2, Muhammad Junaid1,3, Naima Hamid1,3
1School of Public Health and Management, Chongqing Medical University, Chongqing 400016, China.
Abstract:
Glioma, a kind of central nervous system (CNS) tumor, is hard to cure and accounts for 32% of all CNS tumors. Establishing a stable glioma model is critically important to investigate the underlying molecular mechanisms involved in tumorigenesis and tumor progression. Various core signaling pathways have been identified in gliomagenesis, such as RTK/RAS/PI3K, TP53, and RB1. Traditional methods of establishing glioma animal models have included chemical induction, xenotransplantation, and genetic modifications (RCAS/t-va system, Cre-loxP, and TALENs). Recently, CRISPR/Cas9 has emerged as an efficient gene editing tool with high germline transmission and has extended the scope of stable and efficient glioma models that can be generated. Therefore, this review will highlight the documented evidence about the molecular characteristics, critical genetic markers, and signaling pathways responsible for gliomagenesis and progression. Moreover, methods of establishing glioma models using gene editing techniques and therapeutic aspects will be discussed. Finally, the prospect of applying gene editing in glioma by using CRISPR/Cas9 strategy and future research directions to establish a stable glioma model are also included in this review. In-depth knowledge of glioma signaling pathways and use of CRISPR/Cas9 can greatly assist in the development of a stable, efficient, and spontaneous glioma model, which can ultimately improve the effectiveness of therapeutic responses and cure glioma patients.
Insights
This review explores glioma, a challenging brain tumor, and highlights how CRISPR/Cas9 gene editing advances the creation of stable models. These models are crucial for understanding glioma development and improving patient treatment outcomes.
Area of Science:
- Neuro-oncology
- Genetics
- Molecular Biology
Background:
- Glioma represents a significant portion of central nervous system (CNS) tumors, posing substantial treatment challenges.
- Understanding the molecular mechanisms driving glioma tumorigenesis and progression is critical for developing effective therapies.
- Key signaling pathways implicated in gliomagenesis include RTK/RAS/PI3K, TP53, and RB1.
Purpose of the Study:
- To review the molecular characteristics, genetic markers, and signaling pathways involved in glioma.
- To discuss established and emerging methods for creating stable glioma models, with a focus on gene editing techniques.
- To explore therapeutic strategies and future research directions for glioma, particularly leveraging CRISPR/Cas9 technology.
Main Methods:
- Review of existing literature on glioma molecular biology and animal models.
- Analysis of gene editing technologies, specifically CRISPR/Cas9, for glioma model generation.
- Discussion of signaling pathways and genetic markers critical to gliomagenesis.
Main Results:
- CRISPR/Cas9 offers an efficient method for generating stable and effective glioma models.
- Detailed understanding of molecular pathways and genetic markers is essential for glioma research.
- Advancements in model systems are paving the way for improved therapeutic interventions.
Conclusions:
- CRISPR/Cas9 gene editing significantly enhances the development of stable and spontaneous glioma models.
- Improved glioma models are vital for advancing therapeutic responses and patient outcomes.
- Further research into gene editing applications holds promise for conquering glioma.
