Cancer stem cell plasticity drives therapy resistance in colorectal cancer

Table 2 Emerging therapeutic strategies targeting colorectal cancer stem cells

Therapeutic strategy	Primary target	Proposed mechanism	Current status
Wnt inhibitors	Wnt/β-catenin	Reduce CSC self-renewal	Preclinical/early clinical
Notch inhibitors	Notch signaling	Promote CSC differentiation	Clinical evaluation
PI3K/AKT inhibitors	PI3K/AKT pathway	Inhibit survival signaling	Clinical evaluation
HDAC inhibitors	Histone acetylation	Reverse stemness-associated epigenetic changes	Clinical trials
DNMT inhibitors	DNA methylation	Restore differentiation programs	Clinical trials
Immune checkpoint inhibitors	PD-1/PD-L1	Enhance anti-tumor immunity	Approved for MSI-H CRC
Exosome-based therapies	CSC communication	Drug delivery and microenvironment modulation	Experimental

CSC: Cancer stem cell; PI3K: Phosphoinositide 3-kinases; AKT: Protein kinase B; HDAC: Histone deacetylase; DNMT: DNA methyltransferase; PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; MSI-H: Microsatellite instability-high; CRC: Colorectal cancer.