Cancer Stem Cells
235
Platinum-based chemotherapy is curative
in the majority of these patients; how-
ever, many patients are left with residual
masses. The immature cancer cells have
been eliminated by the chemotherapy,
leaving only differentiated cancer cells,
in a mature teratoma. Patients with ma-
ture teratomas rarely develop metastases;
most are cured. This demonstrates that
the elimination of the presumed stem cell
population is sufFcient for curing this solid
cancer.
7
Future Implications of Cancer Stem Cells
The ability to prospectively identify cancer
stem cells should have exciting implica-
tions for the development of new diagnos-
tic tools and therapeutic agents. Currently,
all of the cancer cells within a tumor are
treated equivalently in their presumed abil-
ity to drive tumor growth, invade, and
metastasize. The ability to identify these
crucial cells will allow efforts to develop
novel diagnostics and therapies focused on
the cells responsible for the maintenance
of the malignancy – the cancer stem cells.
±or example, immune therapy efforts to
identify genes and proteins expressed by
cancer cells presently use either whole tu-
mors or all of the phenotypically diverse
cells within a tumor. Since the cancer
stem cells represent only a minority of
the cancer cells in most tumors, it is nearly
impossible to identify diagnostic markers
or therapies that target these cells without
their puriFcation. However, directing ex-
pression analysis to enriched populations
of cancer stem cells would allow the iden-
tiFcation of novel diagnostic markers and
therapeutic targets that can be exploited
to more effectively diagnose and treat pa-
tients. This principle is illustrated by the
observation that the BCR/ABL oncogene
mRNA appears not to be expressed by
HSCs that carry the mutation in their
DNA; therefore, efforts to eradicate the
cancer by targeting the BCR/ABL protein
might fail to target the cancer stem cells.
As illustrated above for AML-initiating
cells, the ability to prospectively identify
cancer stem cells should also improve our
ability to evaluate the curative potential of
new therapeutic agents. Although cancer
cell lines are useful for the evaluation of
particular biochemical pathways, they have
proven somewhat unreliable when used to
predict the clinical efFcacy of a particular
therapeutic agent in patients. These cell
lines are relatively homogeneous, and even
tumors grown using these cell lines are
homogeneous. This contrasts sharply with
the phenotype of real tumors. However,
tumors that are grown in the immunod-
eFcient mouse model of human cancer
appear to more closely recapitulate the phe-
notypic diversity of patients’ original tu-
mors, including the generation of both tu-
morigenic and nontumorigenic cells. This
model might therefore more effectively
predict the potential usefulness of a partic-
ular therapeutic agent. New agents could
be tested for their ability to eliminate the
tumorigenic (cancer stem cell) component
of tumors from multiple patients, allowing
the agents with the greatest curative poten-
tial to proceed to human clinical trials.
See also
Developmental Cell Biol-
ogy; Genetics, Molecular Basis of.
Bibliography
Books and Reviews
Cotta, C., Swindle, C., Weissman, I.L., Klug, C.A.
(2001) in: Klug, C., Jordan, C. (Eds.)
Retroviral
previous page 909 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online next page 911 Encyclopedia of Molecular Cell Biology and Molecular Medicine read online Home Toggle text on/off