articleMolecular CancerJan 22, 2026GOLD OA

Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials

Hubei University of Medicine · Union Hospital · +5 more institutions

PubMed
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Abstract

Colorectal cancer (CRC) remains a major global health burden, with therapeutic resistance accounting for the majority of treatment failures and cancer-related deaths. Cancer stem cells (CSCs), which possess intrinsic drug tolerance and self-renewal capacity, drive both primary and acquired resistance. CSCs maintain drug tolerance through the activation of core signaling cascades, including Wnt/β-catenin, Notch, Hedgehog, PI3K/Akt, and MAPK/ERK pathways, as well as through epithelial-mesenchymal transition (EMT), enhanced DNA repair, and PD-1/PD-L1-mediated immune evasion. These molecular alterations transform the tumor microenvironment (TME) into a stemness-supportive, immunosuppressive niche, thereby…

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