Stem cells are noted by two primary characteristics: the ability to renew themselves by cell division, and to differentiate into a wide range of specialized cells. They are under tight biological control, with a balance between self-renewal and differentiation. Cancer stem cells have similar processes, but these processes are abnormal and unregulated. Reya
Where do Cancer Stem Cells Come From?
Tumors consist of a heterogeneous group of cells as a result of accumulated mutations. Controversy exists within the scientific community if cancer stem cells can even be isolated and characterized. Several hypotheses have been brought forward to account for the appearance of cancer stem cells:
- Cancer stem cells could arise from normal stem cells. Since stem cells are long-lived, there is ample opportunity for multiple mutations to arise, eventually to lead to cancerous cells.
- Cancer stem cells could arise from so-called progenitor cells. Progenitor cells are further along in development than stem cells, and can only differentiate into a specific type of cell. In this sense, progenitor cells can be thought of as intermediate between stem cells and the final differentiated cells.
- Finally, cancer stem cells could result from mature, differentiated cancer cells that revert back to stem cells, but maintain their cancerous nature.
What is the Significance of Cancer Stem Cells?
Proponents of the cancer stem cell hypothesis state that tumors consist of two types of malignant cells. Most of the tumor consists of rapidly growing cells that are hypersensitive to certain biochemical signals that lead to proliferation. A much small number of cancer stem cells are also present that are more quiescent, long-lived and not as sensitive to these signals. Cancer treatments usually focus on attacking the rapidly growing cells. The tumor shrinks, and the patient appears to be cured. However, the cancer stem cells manage to survive the treatment, multiply, and the cancer recurs. This newly recurred cancer is now resistant to all treatments, and the cancer spreads.
Knowledge of Cancer Stem Cells Leads to More Effective Treatments
The majority of cancer treatments are targeted at rapidly dividing cells that are more sensitive to the treatments than normal cells. However, stem cells (and presumably cancer stem cells) are naturally resistant to chemotherapy. The cells are able to pump out toxic drugs, they have proteins to repair their DNA damaged by the drugs, and have a slow rate of cell turnover. The challenge for researchers will be to identify unique biochemical pathways of cancer stem cells. Behbod The technique of gene expression profiling can be important in this regard.
The most effective treatments for cancer may be with a combination of drugs that target both the rapidly growing cells, and the much smaller number of cancer stem cells.
Recent Advances in Cancer Stem Cell Research
The Broad Institute is a Harvard-MIT collaborative for genomics research. The August 14, 2009 issue of the New York Times reported on their researchers’ recent findings that were published in the journal Cell. The researchers screened some 16,000 chemicals, and found 32 that selectively targeted cancer stem cells. Although the chemicals may not prove to be good treatments for cancer, they illustrate confirmation of the concept of cancer stem cells.
OncoMed Pharmaceuticals reported in Cell Stem Cell on their research in developing a monoclonal antibody that targets cancer stem cells by reducing cell frequency, and by disrupting angiogenesis (blood vessel formation in the tumor). The researchers found that using the antibody (particularly in combination with chemotherapy) significantly reduced cancer recurrence. The company is developing other monoclonal antibodies for this purpose.
Cancer Stem Cells: Increasing our Knowledge of the Cancer Process
Cancer stem cells have characteristics similar to normal stem cells, but are unregulated. The cancer tumor may consist of a large number of rapidly growing cells, and a much smaller number of cancer stem cells that are quiescent and long-lived. In order to be successful, treatment procedures must must attack both the rapidly growing cells and cancer stem cells.
References
- Behbod, F. and Rosen, J. Will Cancer Stem Cells Provide New Therapeutic Targets? Carcinogenesis. 2004, 26:4, 703-711.
- Sagar, J., et.al. Role of stem cells in cancer therapy and cancer stem cells: a review. Cancer Cell International. 2007, 7:9
- Reya, T., et.al. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov., 414 (105-111)
- Wade, N. New Screening Could Lead to More Potent Cancer Drugs. The New York Times. August 14, 2009.
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