Metastatic cancer stem cells: A new target for anti-cancer therapy?

Abstract

Over the past few years, supporting evidence for the cancer stem cell hypothesis has been provided for an increasing number of tumor entities. According to this hypothesis, only a small population of undifferentiated cells with stem cell characteristics has the ability to form tumors through asymmetric division and subsequent differentiation of the progeny into the heterogeneous cell types that comprise a tumor. Recently, we were able to show that cancer stem cells are not only responsible for tumorigenesis, but that they contain a subpopulation characterized by CXCR4 expression which is exclusively capable of disseminating and subsequently providing the substrate for tumor metastasis. Of note, these recent advances in our understanding of cancer stem cell biology raise more questions than they answer. Some of these arising questions regarding the targeted elimination of these cancer stem cells will be addressed in this perspective.

Exploring cancer stem cell niche directed tumor growth

“…7,8 It is believed, for instance, that the CSCs that fuel tumor growth are more therapy resistant and form the seeds of metastasis, they should therefore be effectively targeted by every successful anti-cancer therapy. 7,9 In the CSC model of malignancies tumors are viewed as hierarchically Exploring cancer stem cell niche directed tumor growth Andrea …”

Targeting prostate cancer based on signal transduction and cell cycle pathways

“…These cells are also more commonly referred to in other types of cancer as tumor stem cells or cancer-initiating cells. [340][341][342][343][344][345][346] Radiation therapy creates substantial DNA damage that is recognized by p53 and forces most cells to either undergo programmed cell death (e.g., apoptosis), necrosis or enter a state of reproductive death (i.e., cellular senescence). Radiation therapy is conventionally delivered in fractions of 1.8-2.0 Gy doses for 5 days a week until a total of 60-80 Gy is reached.…”

Prostate Cancer Stem Cells and Their Involvement in Metastasis

“…Also, the CD133 -colon cancer cells have been shown to be even more aggressive and metastatic than their CD133 + counterparts although both populations could initiate tumor development (Shmelkov et al, 2008). These findings suggest that metastasis and tumor initiation might be processes mediated by distinct cancer cell populations (Hermann et al, 2008) and there might exist metastatic CSCs (Mimeault and Batra, 2007;Weigelt et al, 2005). The genetically-based clonal evolution hypothesis proposes that metastasis results from accumulation of genetic mutations and only the rare tumor cell clones that have attained the right and sufficient numbers of mutations will be "naturally selected" and able to disseminate (Campbell and Polyak, 2007;Polyak, 2007).…”

“…In figure 1.3B, an example on breast cancer is given to illustrate the hypothesis of CSC generating tumor heterogeneity. In CSC based tumor therapy, when CSCs are eliminated, tumor development will be halted and tumor recurrence will not occur (Hermann et al, 2008). One significant point between these two models is that clonal evolution mainly depends on intrinsic genetic changes to undergo natural selection whereas CSC tumor phenotype is determined by a combination of genetic and epigenetic events.…”

“…In other words, the CSC hypothesis will be considered incomplete without making connection to metastasis (Hermann et al, 2008;Hurt and Farrar, 2008;Li et al, 2007b;Wicha, 2006). In fact, many pieces of evidence support CSC involvement in metastasis.…”