Cancer stem cells (CSCs) constitute a small but critical subpopulation within tumors that possess stem cell-like properties, including self-renewal, pluripotency, and the ability to differentiate into diverse cancer cell types. These unique characteristics enable CSCs to drive tumorigenesis, sustain tumor heterogeneity, and promote metastasis. The hierarchical or CSC model posits that tumors are organized with CSCs at the apex, responsible for continuous tumor growth and regeneration, while their differentiated progeny form the bulk of the tumor mass but lack long-term proliferative capacity. This model contrasts with the stochastic model of tumor propagation and provides a framework for understanding intratumoral heterogeneity and therapeutic resistance.

Biological properties and Clinical implications 

CSCs exhibit enhanced capabilities to initiate tumor growth, invade surrounding tissues, migrate, and resist conventional therapies such as chemotherapy and radiation. Their intrinsic resistance mechanisms contribute to tumor relapse and metastasis, making CSCs a pivotal target for novel anti-cancer therapies. Commonly used markers for CSC identification include CD133, CD44, ALDH1A1, CD34, and EpCAM, which help isolate these cells from both solid and hematological malignancies. Regulatory networks involving signaling pathways such as Wnt/β-catenin, Notch, and Hedgehog, along with microRNA modulation and epithelial-mesenchymal transition (EMT), govern CSC maintenance and plasticity.

Therapeutic strategies targeting CSCs are emerging, including monoclonal antibodies, tyrosine kinase inhibitors, CAR T-cell therapies, and tumor vaccines, aiming to eradicate the CSC population and prevent tumor recurrence. Despite advances, challenges remain in definitively defining CSC populations across cancers and overcoming their heterogeneity. Personalized treatment approaches based on molecular profiling of CSCs hold promise for improving patient outcomes, especially in metastatic and treatment-resistant cancers.