Biomedical Engineering Reference
In-Depth Information
chemotherapeutic agents and radiotherapy have provided a novel direction of
research for the development of future drugs.
8.1 Minimal Residual Disease
The cancer stem cell model could be an elegant explanation for a frequent
clinical observation referred to as minimal residual disease (MRD) (Al Hajj
et al., 2004; Jordan et al., 2006). The tumor mass responds very well to admi-
nistered chemotherapy and no clinical signs of remaining tumor material are
present, but after cessation of therapy the tumor rapidly re-grows. This effect is
potentially caused by rapid tumor cell outgrowth from a small population of
cancer stem cells that evaded the therapeutic regime and were capable of re-
growing the original malignancy, while the bulk of the non-cancer stem cell
tumor cells responded very well to the therapy. In a study using human color-
rectal cancer xenografts in mice a clear increase in the percentage of CD133
+
cells is observed under oxaliplatin treatment, providing experimental evidence
for the proposed resistance of cancer stem cell compared to their differentiated
counterparts (Todaro et al., 2007a).
We are only at the very beginning of understanding the nature of this relative
chemo- and radio-resistance. The mechanisms involved in the cancer stem cell-
specific therapy resistance, for other malignancies than colorectal cancer, are
expression of multidrug resistance (MDR) proteins, differences in DNA repair
mechanisms, differential sensitivity to apoptosis-inducing signals, and the pos-
sible quiescent state of the cancer stem cell compartment (Dean et al., 2005).
8.2 Chemoresistance of Colon-Cancer Stem Cells
It has recently been shown that IL-4 protects colon-cancer stem cells from the
induction of apoptosis by chemotherapeutic agents in vitro and in vivo. Anti-
IL-4 therapy resulted in in vivo sensitization of the colon-cancer stem cell to
therapy with oxaliplatin (Todaro et al., 2007a). This illustrates how future
therapeutic modalities might be developed; an agent that sensitizes or differ-
entiates the cancer stem cells is combined with a chemotherapeutic agent that
effectively kills the tumor cells, including the cancer stem cell compartment.
This strategy prevents the cancer stem cells from surviving the therapy and
effectively growing back the tumor.
8.3 Development of New Therapies
The cancer stem cell theory also implies that the way we approach the clinical
testing of new drugs to treat malignancies has to be reconsidered. If indeed the
