Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications
Simple Summary Colorectal cancer is often driven by a small population of colorectal cancer stem cells (CCSCs) that fuel tumor growth, metastasis, and treatment resistance, leading to relapse. These CCSCs are regulated by key signaling pathways, including Wnt/β catenin, Notch, Hedgehog, PI3K/AKT, MAPK/ERK, NF-κB, and TGF β, which are now being targeted by emerging drugs. CCSC markers and gene signatures are also under study as diagnostic and prognostic tools for early detection, minimal residual disease monitoring, and outcome prediction, although robust CCSC-specific assays and prospective clinical validation are still lacking. However, translating CCSC directed therapies into safe and effective treatments is difficult due to tumor heterogeneity, CCSC plasticity, compensatory pathways, and overlap with normal intestinal stem cell regulation. This review outlines CCSC biology, their biomarker potential, and current clinical trials targeting CCSC associated pathways, while highlighting major translational barriers that must be overcome.