Cancer stem cell plasticity drives therapy resistance in colorectal cancer

Table 1 Major colorectal cancer stem cell markers and their biological significance

Marker	Biological function	Clinical significance
CD133	Stem cell maintenance, tumor initiation	Associated with poor prognosis and chemoresistance
CD44	Cell adhesion, migration, CSC maintenance	Promotes invasion, metastasis, and therapy resistance
LGR5	Intestinal stem cell marker, Wnt signaling	Drives tumor initiation and regeneration
ALDH1	Detoxification and stem cell metabolism	Correlates with CSC enrichment and poor survival
EpCAM	Cell adhesion and proliferation	Frequently expressed in colorectal CSC populations

CSC: Cancer stem cell; LGR5: Leucine-rich G repeat-containing protein-coupled receptor 5; ALDH1: Aldehyde dehydrogenase 1; EpCAM: Epithelial cell adhesion molecule.

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.