Introduction & background
Classical markers and signaling pathways of PCSCs
Markers
Name | Functions on PC and major associated signaling pathways |
---|---|
Cell surface markers | |
CD24 | JADE dependent AKT/mTOR pathway; SHH pathway |
CD44 | JADE dependent AKT/mTOR pathway; SHH pathway; SPP1/CD44 pathway; CD44/ITGB1 pathway; Wnt pathway; |
ESA/EpCAM | SHH pathway; Wnt pathway |
CD133 | CCL21/CCR7 axis |
CXCR4 | SDF-1/CXCR4 axis |
nestin | TGFβ/SMAD4 pathway |
c-MET | YAP/HIF-1α axis |
NANOG | Wnt pathway; NOTCH pathway; SHH pathway |
OCT4 | SHH pathway; Wnt pathway; NOTCH pathway |
NOTCH1 | NOTCH1/Jagged1/Hes1 axis |
SOX2 | FGFR/AKT/SOX2 axis |
Tspan8 | SHH pathway |
α6β4 | Form hemidesmosomes |
DCLK1 | Regulate miRNAs; Histone modification |
CD9 | Modulate glutamin metabolism |
GLRX3 | Met/PI3K/AKT; Combine with CA19-9 increase the sensitivity of diagnosis |
Side population and drug efflux markers | |
ABCB1 | Not reported |
ABCG2 | ERK1/2/HIF-1α axis |
CD31 | Not reported |
CD45 | Not reported |
Intracellular markers | |
ALDH1 | Wnt |
LGR5 | Not reported |
Signaling pathways and targeted therapy
Major signaling pathways
Targeting stemness-related pathways in PC
Category | Drug | Drug development stage | Treatment |
---|---|---|---|
Sonic Hedgehog (SHH) pathway inhibitor | Smo inhibitor | ||
Cyclopamine | Preclinical | ||
Sonidegib | Phase 2 (NCT02358161) | Sonidegib + Gemcitabine + Nab-paclitaxel | |
Gli inhibitor | |||
α‐Mangostin | Preclinical | ||
GANT-61 | Preclinical | ||
Notch pathway inhibitor | γ- secretase inhibitors (GSI) | ||
MK0752 | Phase 1 (NCT01098344) | Gemcitabine Hydrochloride + MK0752 | |
PF-0308401 | Phase 2 (NCT02109445) | Gemcitabine + Nab-Paclitaxel + PF-03084014 | |
MRK-003 | Preclinical | ||
Quinomycin | Preclinical | ||
Genistein | Phase 2 (NCT00376948) | Gemcitabine + Erlotinib + Genistein | |
Curcumin (Diferuloylmethane) | Phase 1 (NCT02336087) | Gemcitabine Hydrochloride + Paclitaxel Albumin + Metformin Hydrochloride + a Standardized Dietary Supplement (including curcumin) | |
Curcumin | |||
Gemcitabine + Curcumin | |||
Gemcitabine + Curcumin + Celebrex | |||
Phase 2 (NCT00094445) | |||
Phase 2 (NCT00192842) | |||
Phase 3 (NCT00486460) | |||
Quercetin | Preclinical | ||
Cimigenoside | Preclinical | WNT974 (LGK974) + PDR001 | |
Salinomycin | Preclinical | ||
PORCN inhibitor | OMP-18R5 + Nab-Paclitaxel + Gemcitabine | ||
Wnt/β-catenin pathway inhibitor | WNT974 (LGK974) | Phase 1 (NCT01351103) | |
FZD antagonist | |||
OMP-18R5 | Phase 1 (NCT02005315) | ||
LRP inhibitor | pyrvinium | ||
Salinomycin | Preclinical | ||
β-catenin-destruction complex antagonist | |||
pyrvinium | Phase 1 (NCT05055323) | Genistein + Gemcitabine + Erlotinib | |
β-catenin transcriptional activity inhibitor | |||
FH535 | Preclinical | ||
Genistein | Phase 2 (NCT00376948) | ||
Lycopene | Preclinical | ||
Piperine | Preclinical |
Transcription factors | PAF1, EHF, SNAI2 |
---|---|
Epigenetic regulators | FTO, SIRT1, CRL4B, MBD3, UCHL5, GALNT3, B3GNT3, EZH2, BMI-1 |
Metabolic regulators | OPA1, DRP1, MYC, PGC-1α, LKB1, PGC-1β, NAF-1 |
Signaling pathway regulators | Tetraspanin-8, FAM83A, RER1 |
MicroRNAs (miRNAs) | OncomiRNAs: miR-10b, miR-17-5p, miR-21, miR-27a, miR-221, miR-338-5p, miR-520 h, miR-1246 Tumor suppressor miRNAs: miR-34a, miR-101, miR-145, miR-146a, miR-146b-3p, miR-183, miR-200a/c, miR-203, miR-429 |
Long non-coding RNAs (lncRNAs) | GAS5, HOTAIR, XIST, DYNC2H1-4 |