Biomedical Engineering Reference
In-Depth Information
15 Future Research
The identification of cancer stem cells in solid tumors has important implica-
tions for basic cancer research. Most analyses of tumors such as gene expres-
sion, microarray, proteomic, and many phenotypic assays have been performed
on whole tumors and have not revealed data on the small fraction of tumor stem
cells. In addition, screens for cancer cytotoxic drugs have involved cell cultures
treated over short time periods (Alley et al., 1988). Drugs specifically targeting
cancer stem cells may display modest activity in short-term proliferation assays
and be rejected for further follow-up study in animals or humans.
Several important questions remain from the current data. Are current
markers for cancer stem cells adequate? Do the side population cells isolated
from cell lines (Hirschmann-Jax et al., 2004; Kondo et al., 2004) bear a relation-
ship to cancer stem cells? In principle in any permanent cell line there must be
self-renewing cell population. If the characterization of the SP cells in cell lines
could be applied to cancer stem cells, this could advance understanding rapidly.
One property of cancer cells is the ability, like stem cells, to grow in soft agar
cultures (Hamburger and Salmon, 1977). It has been found that only a fraction
of cells in a tumor cell culture can form a colony in soft agar. Are the cells
forming soft agar colonies cancer stem cells? This would be a logical conclusion
from the information at hand. It is known that the clonogenicity varies sub-
stantially between different tumor cell lines. If clonogenicity is related to self-
renewing cells in the culture then assays based on colony formation may be
useful for screening for stem-cell-targeting therapies. Such assays would be
more time consuming and have a lower throughput, but might in the end
prove more informative.
16 Conclusions
The identification of cancer stem cells in certain solid tumors has created
considerable excitement in the field and generated new research possibilities.
If these results can be extended to most or all cancer cell types, a considerable
advancement in understanding will be achieved. Separating the cancer process
into a stem cell activation phase and a tumor progression phase allows an
understanding of how the myriad cancer causing agents can have their effect
on specific tissues. Research efforts directed to understand the growth require-
ments of tumor stem cells as well identify tumor stem cell antigens could lead to
new targeted approaches.
The isolation and characterization of cancer stem cells from other tissues will
be a great aid in cancer diagnostics, cancer prevention, and therapeutics.
Normal stem cell-based approaches are being intensively developed as an aid
in replacing damaged cells and tissues in the body. The insight from the growth
and characterization of normal stem cells will aid in the understanding of cancer
stem cells and in new therapeutic approaches.
