Biomedical Engineering Reference
In-Depth Information
the properties of in vivo CSCs, the challenges investigators currently face due to
low numbers of cells will be overcome. Techniques studying self-renewal cur-
rently involve serial transplantation of tumor cells. While this demonstrates the
retained ability of the cells to initiate a tumor, the method is lengthy, indirect, and
does not readily allow for the study of the processes that govern self-renewal.
The cell of origin is also an important topic that needs continued exploration.
Does the CSC arise from a normal SC? If so, what is the switch(es) that turns a
normal SC into a CSC? Likewise, if the CSC instead arises from a TA cell, what
change(s) occurred that allowed the TA to regain the ability to self-renew?
Thus, an understanding of not only the pathways governing both self-renewal
and differentiation but also the understanding of how this balance is main-
tained will be important for understanding the etiology of prostate cancer.
With an understanding that prostate cancer develops from a CSC rather than
from the transformation of any cell within the prostate, the therapeutic strategies will
need to switch focus onto the CSCs specifically. Traditional therapies, for the most
part, rely on both the removal of androgen as a stimulus and the ablation of rapidly
cycling cells that have a limited ability to repair DNA. Given that the CSC is neither
AR
+
nor a fast-cycling cell, new therapies directed at the CSC need to be developed.
The ability to do high-throughput screens is also challenging given the low numbers
of CSCs that can be isolated using current techniques. Therefore, the understanding
of the pathways and biology unique to CSCs that allow for their maintenance is of
paramount importance so that more targeted therapies can be derived.
7 List of Abbreviations
RNASEL:
ribonuclease L
L HPIN:
high-grade pre-neoplastic lesion prostatic intra-epithelial neoplasia,
ADT:
androgen deprivation therapy,
GnRH:
gonadotropin-releasing agonists,
LH:
luteinizing hormone,
CPRC:
castrate-resistant prostate cancer,
AR:
androgen receptor,
PZ:
peripheral zone,
CZ:
central zone,
TZ:
transition zone,
K:
cytokeratin,
CSC:
cancer stem cell,
AML:
acute myelogenous leukemia,
NOD/SCID:
non-obese diabetic and severe combined immunodeficiency,
SC:
stem cell,
TA:
transit-amplifying,
PSA:
prostate-specific antigen,
PAP:
prostatic acid phosphatase,
