Читать книгу The SAGE Encyclopedia of Stem Cell Research - Группа авторов - Страница 278

If cancer stem cells are the primary driver of cancer growth and metastasis, then effective cancer treatments must attack the CSCs in addition to eliminating the bulk of the tumor. Shrinking a cancerous tumor or reducing leukemic cells in the blood may offer temporary relief, but it will not offer a long-term cure if CSCs are not eliminated. Furthermore, if only the CSCs are eliminated, the rest of the cancer cells in the body might be attacked by the immune system or die out naturally. The most effective cancer treatments, therefore, will be those that specifically target CSCs. Discovering such treatments will require that we know as much as possible about the qualities and behavior of CSCs.

Figure 5 Both tumor models may play a role in the maintenance of a tumor. Initially, tumor growth is assured with a specific CSC (CSC 1). With tumor progression, another CSC (CSC 2) may arise due to the clonal selection. The development of a new more aggressive CSC may result from the acquisition of an additional mutation or epigenetic modification.

Researchers at Stanford’s Ludwig Center for Cancer Stem Cell Research and Medicine, for instance, discovered why stem cells, including cancer stem cells, are resistant to the ionizing radiation used in many cancer treatments. This understanding may help researchers find compounds that make CSCs vulnerable to radiation damage. Another example concerns immune therapies in which the body’s immune system is trained to attack cancer cells. Some of these therapies failed in clinical trials of skin cancer, and Stanford researchers demonstrated why: the targets that the immune system were trained to attack belonged not to the CSCs but to slightly different daughter cells. The immune therapies seemed effective at first as they attacked the daughter cells, but they left the skin cancer stem cells untouched and therefore it could not cure the cancer.

The first conclusive evidence for CSCs was published in 1997 in Nature Medicine. Bonnet and Dick isolated a subpopulation of leukemic cells that expressed a specific surface marker CD34, but lacked the CD38 marker. The authors established that the CD34+/CD38– subpopulation is capable of initiating tumors in NOD/SCID mice that are histologically similar to the donor. The first evidence of a solid tumor cancer stem–like cell followed in 2002 with the discovery of a clonogenic, sphere-forming cell isolated and characterized from human brain gliomas. Some researchers favor the theory that the CSC is generated by a mutation in stem cell niche populations during development. These developing stem populations are mutated and then expanded such that the mutation is shared by many of the daughter cells of the mutated stem cell.

Another theory associates adult stem cells with the formation of tumors, most often in tissues with a high rate of cell turnover (such as the skin or gut). In these tissues, stem cells are thought to be responsible for tumor formation as a result of the frequent cell divisions of these stem cells (compared to most adult stem cells) in conjunction with the extremely long life span of adult stem cells. This combination creates the ideal set of circumstances for mutations to accumulate; accumulation of mutations is the primary factor that starts a cancer. Another theory is that the mutated cells de-differentiate into stem cells.