Focusing on Cancer Stem Cells
Many solid tumors appear to have a small population of stem cells that are partially resistant to chemotherapy and can perpetuate themselves indefinitely. These cancer stem cells thus far have been isolated from breast and brain tumors as well as blood. The exact origin of these cancer stem cells remains to be defined.
With mounting evidence to support the hypothesis that genetic alterations in tissue stem cells may represent the origins of some cancers, the time is right to more vigorously explore the properties, mechanisms, and vulnerabilities of this subset of cells. The presence of such cells, first demonstrated in acute myeloid leukemia patients, provides a different and exciting model with which to further explore cancer biology.
As a result, NCI is establishing a trans-NIH group of scientists interested in embryogenesis and cancer stem cell biology to advance the study of the underlying mechanisms in these processes. Establishing this group will facilitate the sharing of data, reagents, and animal models, and also provide a meaningful scientific interface with similar groups of extramural scientists.
Isolating and studying cancer stem cells should give us new insights into cancer and therapies. A defining characteristic of cancer stem cells is their ability to self-renew while giving rise to a diverse population of cells. In this respect, cancer stem cells are like embryonic stem cells, and the lessons of embryology, in which the role of stem cells are well defined, are crucial to understanding their role in carcinogenesis.
The mechanisms that allow controlled growth and migration of cells during the development of complex organisms from a single cell may be the same genetically programmed signal pathways that, when left unregulated in the adult organism, allow the development of tumors. Tumors are, in essence, complex "organs" complete with neovasculature and phenotypically altered supporting tissues.
Relatively little is known about the mechanisms of self-renewal, but researchers are beginning to identify potential genes and pathways involved. This could eventually lead to targets for intervening in the process, but without disrupting the behavior of normal tissue stem cells.
Some good news in this regard was reported last month. Researchers at the Dana-Farber Cancer Institute found differences between genetic signatures associated with self-renewal in cancer stem cells and in normal blood stem cells in mice. This suggests that it may be possible to target cancer stem cells in humans.
So where do cancer stem cells come from? One theory says they start out as normal stem cells until they become altered and start producing cancer cells. Another says that some more mature, differentiated cells may regain the ability to self-renew through genetic changes - a process of de-differentiation as they become malignant.
There may be evidence for both theories. It's important to remember that these rare cells have only recently been discovered. To answer fundamental questions about them, we need to develop more efficient techniques for isolating the cells and maintaining them in culture, and we need to draw on our knowledge of embryogenesis. Single-cell analyses will likely be needed to distinguish events present in cancer stem cells from the more differentiated cells that make up the majority of the tumor.
I am excited about the formation of this group. We have seen the success of another trans-NIH group in which NCI plays an integral role. The Trans-NIH Angiogenesis Research Program has improved the exchange of information and resources for angiogenesis researchers focused on diverse topics such as macular degeneration, cancer, and heart disease. Likewise, the new group has the potential to advance the science around stem cell biology and bring us closer to new and potentially highly effective therapies in cancer and other diseases.
Dr. John E. Niederhuber