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. 2021 Apr 8;22(8):3863. doi: 10.3390/ijms22083863

Table 1.

Potential therapeutic targets against cancer stem cells.

Cancer Stem Cell Pathway Potential
Therapeutic Target
Agents Effects Target Model References
Notch
pathway
Notch
signaling
Notch-1 siRNA, Delta-like-1 siRNA, Jagged-1 siRNA, Delta-like-1 Fusion protein Downregulation of Notch and its ligands leads to a reduction of oncogenic potential of GSCs GBM cell lines [80,81]
Notch
signaling
γ-secretase
inhibitor GSI-18
Inhibition of Notch by GSIs increases neuronal differentiation and decreases tumorigenicity DAOY, PFSK, D283Med, and D425Med cell lines.
HSR-GBM1 and JHH520 GBM neurosphere lines
[82,83]
MRK003
Notch +
autophagy targeting
MRK003 +
chloroquine
Protective autophagy abrogated by combination with chloroquine HSR-GBM1 and JHH520 GBM neurosphere lines [83]
Notch + leptin GSIs + LFDI
peptide
(Leu-Asp-Phe-Ile)
High expression of leptin receptors in tumorspheres from GBM human fetal glial cells SVG p12, human [86]
GBM cell lines
U-87 MG, T98G
Hypoxic
tumor cells
vasorin Vasorin acts triggering Notch under hypoxic conditions GSCs and non-GSCs from GBM [87]
Shh pathway Shh cyclopamine Inhibition of hedgehog pathway by cyclopamine inhibited formation of GBM-derived neurospheres 40–60% reduction in the growth of adherent glioma lines [91]
Wnt pathway GBM differentiation pathway Dickkopf-1 (DKK1) Wnt inhibitor suppress PLAGL2 PLAGL2 acts as an oncogene in human GBM regulating Wnt signaling primary GBM and established glioma cell lines [92]
ASCL1 - ASCL1 and Wnt signaling are connected and collaborate with developmental transcription factors (TFs). They support GSCs’ growth GSC lines derived from different human tumors [93]
RYK
pathway
- RYK promotes stem cell-like and tumorigenic features to glioma cells and are essential to support GSCs GBM cell line U87MG, AM38, and U251MG cells [94]
Wnt/β catenin - Tumor chemoresistance acquisition depends on mesenchymal transformation that is triggered by Wnt/β catenin signaling GSCs [93]
Tumor microenvironment Microvasculature and TAMs Erlotinib and Bevacizumab Bevacizumab treatment reduces the number of CD133+/Nestin+ tumor initiation cells and decreases microvasculature density and tumor growth CSCs obtained from tumors [95]
M2-TAMs and microvasculature BLZ945-Inhibitor
of the CSF-1
receptor (CSF-1R)
TAMs support GBM tumor growth by promoting neovascularization. They play a tumor-supportive role in GBM progression Proneural GBM [96]
TAMs shPOSTN Silencing POSTN that recruits TAMS reduces TAM density, inhibits tumor growth, and increases survival of mice bearing GSC-derived xenografts Human GBM specimens and glioma-derived cells [97]