Overview

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.

Procedure

Most cancers contain a non-uniformly distributed and genetically distinct subpopulation of tumor cells.

Some of these cells, called cancer stem cells, possess the characteristics associated with both cancer cells and stem cells. This means that as well as participating in tumor propagation, such cells can self-renew and differentiate into multiple lineages.

A cancer stem cell, or CSC, can undergo asymmetric cell division - where one set of daughter cells retain the stem-cell potential and can divide indefinitely, while the other can undergo only a few rounds of division before terminally differentiating and eventually dying.

A CSC can also secrete elevated levels of vascular endothelial growth factors within a tumor and generate new blood and lymphatic vessels that maintain a continuous supply of nutrients to the growing tumor.

Additionally, cancer stem cells can attain properties such as increased invasiveness and migration ability, which may aid them in establishment of secondary metastatic sites in the body.

Even though cancer stem cells carry the potential to seed new tumors and drive their growth, it is the rapidly dividing non-stem cells that form major components of the tumor and sustain its growth.

This heterogeneity in the cancer cell population makes it difficult for most cancer therapies to target and get rid of all cancer cells at once.

Moreover, cancer stem cells use survival mechanisms such as increased activation of drug efflux pumps, DNA repair activity, or the expression of detoxification enzymes that help them escape the cancer therapies.

For example, the anticancer drug - imatinib mesylate is frequently used in the treatment of chronic myeloid leukemia. While differentiated cancer cells are sensitive to the drug, cancer stem cells can escape the therapy by exhibiting over-expression of the ABCB1 and ABCG2 membrane transporter proteins.

These proteins help the cells to efflux the drug and reduce its intracellular levels, leading to the generation of resistant cancer cells.

A single surviving cancer stem cell can reestablish the culture, resurrect the disease, and cause tumor relapse.