20.15: Cancer Stem Cells and Tumor Maintenance
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in a quiescent state until the receipt of a stimulatory signal, which triggers proliferation or differentiation. Genetic alterations in these normal stem cells can reprogram their cellular pathways, turning them into cancer stem cells. Such cells divide abnormally and contribute to tumor progression while maintaining their stem cell properties.
Cancer stem cells can give rise to more stem cells or highly differentiated cancer cells with equal probability. While the daughter cancer stem cells can seed new tumors or metastasize to new sites, the non-stem cancer cells terminally differentiate and are eventually discarded and replaced after a few rounds of division. However, in most tumors, the differentiated cells form a significant mass of the cancer-cell population.
Cancer stem cells often demonstrate endurance to conventional cancer therapies. Cancer stem cells' ability to increase drug efflux rate, alter drug metabolism, resist DNA damage, and enhance DNA repair to their advantage, is often attributed to their chemo-resistance. Epigenetic modifications and supplementary survival signals from tumor microenvironments also contribute to the drug resistance exhibited by these cancer stem cells.
Hence, the presence of cancer stem cells is understood to be one of the primary reasons for tumor maintenance, cancer-treatment failure, relapse, and even metastasis.