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.
Article highlights
H3K27me3 misregulation may act as an oncogenic driver in several cancers, and may thus be used as a target for therapy.
H3K27me3 misregulation in cancer is due to a modification in the expression of its writers (mostly EZH2) or erasers (KDM6A and KDM6B).
Logically, if we consider that writers and erasers of H3K27me3 may be targeted for therapy, then readers of this epigenetic mark might also represent rational targets.
The expression of H3K27me3 readers, proteins of the CBX family, are also altered in cancer.
Polycomb-repressive complex 1 (PRC1) and PRC2 complexes responsible for writing and reading H3K27me3 epigenetic mark are implicated in cancer stem cells maintenance.
CBX protein inhibition appears to be a promising anti cancer strategy for targeting cancer stem cells.
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Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose