From: In vitro models of cancer stem cells and clinical applications
Target | Name of drug (synonyms) | Mechanism of action | Ref.(s) |
---|---|---|---|
Microenviroment/Niche | Anti-CD44 monoclonal Abs | CD44 activation | [249] |
Oblimersen sodium (G3139) | Bcl2 antisense oligonucleotyde | [250] | |
AT-101 (gossypol) | Bcl2, Mcl1 inhibitor | ||
ABT-263/ABT-737 | Pan Bcl2 inhibitor | [253] | |
Obatoclax (GX15-070) | [254] | ||
Sabutoclax (Bl-97C1) | [255] | ||
Anti-integrin alfa 6 monoclonal Abs | Block integrin alfa 6 binding | [256] | |
GLPG0187 | Integrin alfa peptide antagonist | [257] | |
EMD 121974 (Cilengitide) | Integrin alfa beta peptide antagonist | ||
Volociximab | Monoclonal antibody targeting integrin alfa beta | [260] | |
ATN-161 | Integrin alfa beta peptide antagonist | [261] | |
Pepducins | CXCR4 antagonist | [262] | |
Plerixafor (AMD3100) | [263] | ||
Neutralizing ab | CXCR4 blocker | [264] | |
Bevacizumab (Avastin) | VEGF-A/VEGFR blocker | ||
Cediranib/AZD2171 | Tyrosine kinase inhibitor VEGFR2 | ||
EphA3 monoclonal Abs | EphA3 blockers | Clinical trial phase I by KloBios Pharmaceuticals | |
Systemic infusion of enzyme PEGPH20 | HA inhibitor | [156] | |
Anthracyclines, EGFR inhibitors, cardiac glycosides, histone deacetylases, HSP90 inhibitors, microtubule targeting agents, proteasome inhibitors, topoisomerase I inhibitors | HIF-1 inhibitors | Reviewed in [158] | |
DNA vaccines | Legumain, Fra-1, Stat3, FAP, HER-2 (CAFs-TAMs) | Reviewed in [138] | |
Monoclonal Ab Sibrotozumab | FAP | ||
PAI-1 | uPA/uPAR inhibitors | Reviewed in [137] | |
Radioactive labeled Ab, siRNA | Tenascin-C | Reviewed in [137] | |
Monoclonal Ab 81C6 | |||
NK4, anti-HGF mAbs | HGF/Met | ||
5-Aza-2΄-deoxycytidine | DNMT1 | [140] | |
MMPs inhibitors | MMPs | ||
Wnt/βcatenin pathway | Anti-Frizzled (Fzd7) monoclonal antibodies (OMP-18R5) | Block formation of active receptor signalling complex; binds 5 Fizzled receptors | |
Truncated Fizzled 8-Fc fusion protein (OMP-54 F28) | Fzd8-Fc selectively binds Wnt ligands | Clinical trial phase I by OncoMed in collaboration with Bayer Pharma AG | |
NSAIDs | COX mechanisms | ||
IWP2 | o-acetyltransferase inhibitor | [271] | |
XAV939 | Tankyrase inhibitor | [272] | |
PKF115-584 | TCF/βcatenin inhibitor | [273] | |
CGP049090 | |||
IWR | Axin stabilizer | [271] | |
ICG-001 | CREB/βcatenin interaction inhibitor | [274] | |
Hedgehog pathway | GANT-61 | Gli DNA binding inhibitor | [173] |
Arsenic trioxide | [174] | ||
BMS-833923 (XL139) | SMO inhibitor | [267] | |
LDE-225 | |||
LEQ506 | |||
PF-04449913 | |||
TAK-441 | |||
Cyclopamine and based compounds | [170] | ||
Vismodegib (GDC-0049) | [275] | ||
mTOR/PI3K/Akt | Perifosine (krx-0401, d-21266) | Akt inhibitor | [276] |
MK-2206 | [277] | ||
GSK690693 | [278] | ||
GSK2141795 | [279] | ||
LY2780301 | [280] | ||
Rapamycin | mTORC1 inhibitor | [281] | |
Temisirolimus (CCl-779) | [282] | ||
Everolimus (SDZ RAD) | [283] | ||
Ridaforolimus (AP23573, MK-8669) | [284] | ||
OSI-027 | mTORC1/2 inhibitor | [285] | |
PP242 | [286] | ||
PP30 | |||
WAY-600 | [179] | ||
WYE-687 | |||
WYE-354 | |||
AZD8055 | [287] | ||
INK128 | [288] | ||
NVP-BKM120 | PI3K inhibitor | [289] | |
PX-866 | [290] | ||
GDC-0941 | [291] | ||
CAL-101 (GS-1101) | [292] | ||
SF1126 | PI3K & mTOR inhibitor | [293] | |
NVP-BEZ235 | [294] | ||
XL765 | [295] | ||
GDC-0980 | [296] | ||
PI-103 | [297] | ||
Metformin | Inhibition of mTOR activation through AMPK | [181] | |
Notch pathway | Anti-Notch 2 and 3 monoclonal Abs (OMP-595R) | Block cleavage of Notch receptor | Clinical trial phase I by OncoMed |
Anti-Notch 1 and 2 monoclonal Abs | [298] | ||
Anti-Notch 3 monoclonal Abs | [299] | ||
Anti-DLL4 (demcizumab) | Block binding of DLLL4 to Notch receptor | Clinical trial phase I by OncoMed | |
Anti-DLL4 monoclonal Abs (OMP-21 M18, REGN421) | |||
DAPT | Gamma-secretase inhibitor | [300] | |
MRK-003 | [301] | ||
LY450139 | [302] | ||
Telomerase | Imetelstat/GRN-163 L | Telomerase inhibitor | Clinical trial phase II by Geron Corporation; [216] |
GRN-163 | Antagonist of telomerase template | [303] | |
Drug efflux | PSC-833 | ABCB1 inhibitor | [304] |
YHO-13351 | ABCG2 inhibitor | [305] | |
Redox balance and metabolism | Genipin | Suppression of UPC2 | [228] |
Phytochemicals | Redox system | ||
Indo-3-carbinol (I3C) | Redox system (stimulates BRCA1) | ||
Genistein | Redox system (ROS scavenger, inhibitor of NFkB, Akt, PTK) | [227] | |
CSC immunogenic responses | CD133 peptide, ICT-121 | Dendritic cell-based vaccine | Clinical trial phase I by ImmunoCellular Therapeutics |
Peptide vaccine (SL401 and SL701) | Interleukin-3 receptor | Clinical trial phase I and II completed by Stemline Therapeutics | |
VS6063 | Focal adhesion kinase (inhibitor) | Clinical trial phase I completed by Verastem and Pfeizer | |
Ipilimumab | CTLA-4 blockers | Clinical trial phase III by BMS/Medarex; [306] | |
TGN1412 | CD28 agonist | ||
MDX-1106 | PD-1 antagonist | ||
Celebrex, Rofecoxib | COX2 inhibitors | Reviewed in [209] | |
CXCR1 blocking Abs or small molecule repertaxin | IL-8/CXCR1 inhibitor | [210] | |
TGF-β type II receptor antibody or SMAD4 siRNA | TGF-β/SMAD 4 | [211] | |
Stemness | BBI608 | STAT3 inhibitor | Clinical trial phase III [135] |
BBI503 | Nanog inhibitor | ||
miRNA based therapies | let-7 anti-sense oligos | H-RAS and HMGA2 | [197] |
miR200c | Bmi-1, ZEB1 | ||
miR-34a | CD44 activation | [202] |