Table 2 Selected clinical therapeutic agents in current cancer stem cell drug treatment

Microenviroment/Niche

Anti-CD44 monoclonal Abs

CD44 activation

[249]

Oblimersen sodium (G3139)

Bcl2 antisense oligonucleotyde

[250]

AT-101 (gossypol)

Bcl2, Mcl1 inhibitor

[251, 252]

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

[258, 259]

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

[151, 265]

Cediranib/AZD2171

Tyrosine kinase inhibitor VEGFR2

[152, 266]

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

Clinical trial phase I [267]; [139]

PAI-1

uPA/uPAR inhibitors

Reviewed in [137]

Radioactive labeled Ab, siRNA

Tenascin-C

Reviewed in [137]

Monoclonal Ab 81C6

Clinical trial phase II [267]; [147]

NK4, anti-HGF mAbs

HGF/Met

[142, 143]

5-Aza-2΄-deoxycytidine

DNMT1

[140]

MMPs inhibitors

MMPs

[141, 268]

Wnt/βcatenin pathway

Anti-Frizzled (Fzd7) monoclonal antibodies (OMP-18R5)

Block formation of active receptor signalling complex; binds 5 Fizzled receptors

Clinical trial phase I by OncoMed; [159, 267]

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

[269, 270]

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)

[160, 267]

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

[225, 226]

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

Clinical trial phase I [267]; [307]

MDX-1106

PD-1 antagonist

Clinical trial phase I [267]; [308]

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

[199–201]

miR-34a

CD44 activation

[202]