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Anoikis resistance as a key driver of glioma malignancy: From ECM detachment to potential druggable targets
Yuheng Zou1, Chen Zou1, Xiumei Huang1
1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Abstract:
Gliomas, particularly glioblastoma multiforme (GBM), represent the most predominant and aggressive primary central nervous system (CNS) tumors, with treatment challenges stemming from their invasiveness and high recurrence. Anoikis is a form of programmed cell death triggered by detachment from the extracellular matrix. Normal cells typically undergo self-elimination, while glioma and other cancer cells often subvert this process through acquired anoikis resistance, enabling sustained anchorage-independent survival and proliferation. This resistance is a key driver of invasion, metastasis, and recurrence. Here, we outline recent advances in morphological and ultrastructural modifications, molecular, and signaling mechanisms governing anoikis and its resistance in malignant cells, with a focus on their specific pathophysiological role in glioma pathogenesis and progression. The experimental platforms are also discussed. Furthermore, we summarize emerging therapeutic strategies targeting anoikis resistance to provide a framework for understanding its contribution to glioma stem cell (GSC) origination, invasion and metastasis, treatment resistance, and recurrence, thereby informing novel therapeutic strategies for GBM and other cancers.
Insights
Glioma cells resist programmed cell death (anoikis), driving tumor growth and recurrence. Targeting this anoikis resistance offers new therapeutic strategies for glioblastoma multiforme (GBM) and other brain cancers.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Cell Death Mechanisms
Background:
- Gliomas, especially glioblastoma multiforme (GBM), are aggressive primary brain tumors with challenging treatments due to invasiveness and recurrence.
- Anoikis, a form of programmed cell death, is typically induced by cell detachment from the extracellular matrix.
- Cancer cells, including glioma cells, often develop resistance to anoikis, enabling survival and proliferation without matrix attachment, which fuels invasion and metastasis.
Purpose of the Study:
- To review recent advances in understanding anoikis and anoikis resistance in malignant cells.
- To focus on the pathophysiological role of anoikis resistance in glioma pathogenesis and progression.
- To summarize emerging therapeutic strategies targeting anoikis resistance for GBM and other cancers.
Main Methods:
- Review of morphological and ultrastructural modifications associated with anoikis resistance.
- Analysis of molecular and signaling mechanisms governing anoikis and its resistance.
- Discussion of experimental platforms used to study anoikis resistance.
- Summary of therapeutic strategies targeting anoikis resistance.
Main Results:
- Anoikis resistance is a critical factor in glioma cell invasion, metastasis, and recurrence.
- Understanding the molecular and cellular mechanisms of anoikis resistance is key to developing effective treatments.
- Emerging strategies focus on overcoming anoikis resistance to target glioma stem cells (GSCs) and improve treatment outcomes.
Conclusions:
- Anoikis resistance significantly contributes to glioma stem cell origination, invasion, metastasis, and treatment resistance.
- Targeting anoikis resistance presents a promising framework for novel therapeutic strategies against GBM and other cancers.
- Further research into anoikis resistance mechanisms can inform the development of more effective treatments for aggressive brain tumors.
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