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Beyond EZH2: is the polycomb protein CBX2 an emerging target for anti-cancer therapy?
Maïka Jangal1, Benjamin Lebeau1, Michael Witcher1
1a The Lady Davis Institute of the Jewish General Hospital, Department of Oncology , McGill University , Montreal , Canada.
Abstract:
Introduction: Epigenetic modifications are important regulators of transcription and appropriate gene expression answering an environmental stimulus. In cancer, these epigenetic modifications are altered, which impact the transcriptome, promoting initiation and cancer progression. Thus, targeting epigenetic machinery has proven to be an efficient cancer therapy. Areas covered: We review CBX2 as a therapeutic target. CBX2 is a polycomb protein, responsible for polycomb-repressive complex 1 (PRC1) targeting to chromatin via recognition of the repressive mark H3K27me3. Mechanistically, CBX2 overexpression may be implicated in poor survival by maintaining cancer stem cells in an undifferentiated state and via repression of tumor suppressors. We discuss strategies used to target CBX proteins and provide insights into biomarker considerations that may be important when targeting CBX family members for anti-cancer therapy. Expert opinion: CBX2 inhibition is a promising approach for the targeting of polycomb complexes in the cancer stem cell niche. However, extensive optimization of the current field of small molecules targeting CBX family proteins will be critical to reach in vivo, or clinical, utility.
Insights
Targeting CBX2, a key epigenetic regulator, shows promise for cancer therapy by impacting cancer stem cells. Further optimization of small molecules targeting CBX proteins is needed for clinical use.
Area of Science:
- Epigenetics and Cancer Biology
- Chromatin Regulation
- Therapeutic Target Identification
Background:
- Epigenetic modifications regulate gene expression and are altered in cancer, driving disease progression.
- CBX2, a polycomb protein, targets polycomb-repressive complex 1 (PRC1) to chromatin via H3K27me3 marks.
- Overexpressed CBX2 may contribute to poor survival by maintaining cancer stem cells and repressing tumor suppressors.
Purpose of the Study:
- To review CBX2 as a potential therapeutic target in cancer.
- To discuss the mechanisms by which CBX2 influences cancer progression.
- To explore strategies for targeting CBX proteins and relevant biomarkers.
Main Methods:
- Literature review of CBX2's role in cancer.
- Analysis of CBX2's mechanism of action in chromatin regulation.
- Discussion of therapeutic strategies and biomarker considerations.
Main Results:
- CBX2 overexpression is linked to poor patient survival.
- CBX2 plays a role in maintaining cancer stem cell populations.
- Targeting CBX proteins presents a promising therapeutic avenue.
Conclusions:
- CBX2 inhibition is a promising strategy for targeting polycomb complexes within the cancer stem cell niche.
- Further development and optimization of small molecules targeting CBX family proteins are essential for clinical application.
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