Longevity & AgingHow Epigenetic Marks Drive Cancer Stem Cells and New Therapeutic Targets
This landmark review from Galassi et al. (2025) examines how epigenetic mechanisms—including DNA methylation, histone acetylation, methylation, and ubiquitination—govern cancer stem cell (CSC) identity across AML, CML, glioblastoma, colorectal cancer, and breast cancer. CSCs are a small, poorly differentiated tumor subpopulation capable of self-renewal, generating differentiated progeny, and resisting therapy. The authors detail how enzymes such as DNMT1, TET2, EZH2, and HDACs maintain stemness programs while suppressing differentiation. Crucially, CSC epigenomes share features with embryonic stem cells rather than adult stem cells. The review also critically evaluates clinical-stage epigenetic drugs—DNMT inhibitors, HDAC inhibitors, EZH2 inhibitors—as strategies to eradicate CSCs, noting both promise and significant challenges including plasticity-driven resistance.
