Table 1 Clinical trials of different strategies for eradicating CSCs
From: The strategies to cure cancer patients by eradicating cancer stem-like cells
Therapies | Agents | Targets | Diseases | Clinical trial ID | Study phase | Ref. |
|---|---|---|---|---|---|---|
Biomarker-targeting strategy | RG7356 | CD44 | Solid tumors | NCT01358903 | Phase I | [109] |
HA-irinotecan | CD44 | Extensive-stage SCLC | / | Phase IIa | [110] | |
CART-CD133 | CD133 | HCC | NCT02541370 | phase II | [118] | |
Curcumin | ALDH | CRC | NCT01490996 | Phase I | [111] | |
Paclitaxel (with reparixin) | ALDH | TNBC | NCT01861054 | Phase II | [112] | |
Disulfiram | ALDH | Germ cell tumor | NCT03950830 | Phase II | [113] | |
Adecatumumab | EpCAM | Hormone refractory prostate cancer | / | Phase I | [114] | |
VB4-845 | EpCAM | Nonmuscle-invasive bladder cancer | / | Phase I | [115] | |
huKS-IL2 | EpCAM | Advanced solid tumors | NCT00132522 | Phase Ib | [116] | |
Catumaxomab | EpCAM | Epithelial cancer | NCT01320020 | Phase I | [117] | |
Pathway-targeting strategy | WNT974 | Porcupine | CRC | NCT01351103 | Phase I | [119] |
Ipafricept (IPA) with nabpaclitaxel/ gemcitabine | FZD | Pancreatic cancer | NCT01351103 | Phase Ib | [120] | |
Vantictumab (OMP‑18R5) with paclitaxel | FZD | HER2-nagetive BC | NCT01973309 | Phase Ib | [121] | |
E7449 | Tankyrase | Advanced solid tumor | NCT01618136 | Phase I | [122] | |
CWP232291 | β-catenin complex | AML | NCT01398462 | Phase I | [123] | |
Acylhydrazones | β-catenin complex | AML | NCT00990587 | Phase I | [124] | |
Cirmtuzumab | ROR1 | Chronic lymphocytic leukemia | NCT02222688 | Phase I | [125] | |
Collagenase (CHH) | YAP | Uterine fibroids | NCT02889848 | Phase I | [126] | |
PF-03084014 | GSIs | Desmoid fibromatosis | NCT00878189 | Phase I | [127] | |
OMP-59R5 | GSIs | Solid tumors | NCT01277146 | Phase I | [128] | |
BMS-986115 | GSIs | Advanced solid tumor | NCT01986218 | Phase I | [129] | |
RO2929097 | GSIs | High grade gliomas | NCT01119599 | Phase 0/I | [130] | |
MK-0752 | GSIs | Pancreatic ductal adenocarcinoma | NCT01098344 | Phase I | [131] | |
RO4929097 (with Vismodegib) | GSIs | Advanced sarcoma | NCT01154452 | Phase Ib/II | [132] | |
LY900009 | GSIs | Advanced-stage cancer | NCT01158404 | Phase I | [133] | |
Demcizumab (with pemetrexed/ carboplatin) | Notch ligand | NSCLC | NCT01189968 | Phase IB | [134] | |
Rovalpituzumab tesirine | Notch ligand | Extensive-stage-SCLC | NCT03033511 | Phase III | [135] | |
Enoticumab | Notch ligand | Advanced-stage solid tumors | NCT00871559 | Phase I | [136] | |
Brontictuzumab | Notch receptor | Solid tumors | NCT01778439 | Phase I | [137] | |
Tarextumab (with etoposide/cisplatin) | Notch receptor | Extensive-stage SCLC | NCT01859741 | Phase II | [138] | |
Vismodegib (GDC-0449) | SMO | Advanced Basal-Cell Carcinoma | NCT00607724 | Phase I | [139] | |
IPI-926 | SMO | Solid tumors | / | Phase I | [140] | |
TAK-441 | SMO | Advanced solid tumors | NCT01204073 | Phase I | [141] | |
PF-04449913 | SMO | Advanced solid tumors | NCT01286467 | Phase I | [142] | |
LDE225 | SMO | Extensive stage SCLC | 01579929 | Phase I | [143] | |
LY2940680 | SMO | Advanced/metastatic cancer | NCT01226485 | Phase I | [144] | |
Sarigegib (with cetuximab) | GLI | Recurrent/metastatic head and neck squamous cell carcinoma | NCT01255800 | Phase I | [145] | |
Itraconazole | GLI | Biochemically relapsed prostate cancer | NCT01787331 | Phase II | [146] | |
AZD9150 | STAT3 | Lymphoma/lung cancer | / | Phase I | [147] | |
OPB-111077 | STAT3 | Advanced Cancers | NCT01711034 | Phase I | [148] | |
Alpelisib | PI3K | Epithelial ovarian cancer | NCT01623349 | Phase Ib | [149] | |
Duvelisib | PI3K | T-cell lymphoma | NCT01476657 | Phase I | [150] | |
TME-targeting strategy | Bintrafusp Alfa | TGF-β/ PD-L | NSCLC | NCT02517398 | Phase I | [151] |
M7824 | TGF-β | Advanced solid tumors | NCT02517398 | Phase I | [152] | |
Galunisertib | TGF-β | Advanced rectal cancer | NCT02688712 | Phase II | [153] | |
FIGHT-101 | FGF/ FGFR | Advanced malignancies | NCT02393248 | Phase I/II | [154] | |
Fruquintinib | VEGF/ VEGFR | metastasis CRC | NCT02314819 | Phase III | [155] | |
Ramucirumab /Pembrolizumab versus Standard of care (SOC) | VEGF/ VEGFR | NSCLC | NCT03971474 | phase II | [156] | |
Rilotumumab (AMG 102) | HGF | NSCLC | NCT02318368 | Phase I/II | [157] | |
Siltuximab | IL-6 | Advanced solid tumors | / | Phase I/II | [158] | |
Immune-targeting strategy | Neo-DCVac | DC | NSCLC | NCT02956551 | Phase I | [159] |
DCs in combination of NAC-AC | DC | Breast cancer | NCT03450044 | Phase I/II | [160] | |
DCs in combination of poly-ICLC | DC | Pancreatic cancer | NCT01410968 | Phase I | [161] | |
DCVax-L plus SOC | DC | Glioblastoma | NCT00045968 | Phase III | [162] | |
Decitabine (with talazoparib) | DNMT | AML | NCT02878785 | Phase I | [163] | |
Azacitidine (with pembrolizumab) | DNMT | Colorectal cancer | NCT02260440 | Phase II | [164] | |
Guadecitabine (with GM-CSF) | DNMT | Advanced colorectal cancer | NCT01966089 | Phase I | [165] | |
Abexinostat | HDAC | Solid tumor malignancies | EudraCT-2009–013691-47 | phase II | [166] | |
Panobinostat | HDAC | AML | / | Phase I | [167] | |
Entinostat | HDAC | HER2 + metastatic BC | NCT02833155 | Phase I | [168] | |
Tazemetostat | EZH2 | B-cell non-Hodgkin lymphoma | / | Phase II | [169] | |
GSK2816126 | EZH2 | solid tumors or B-cell lymphomas | NCT02082977 | Phase I | [170] | |
SHR2554 | EZH2 | Mature lymphoid neoplasms | NCT03603951 | Phase I | [171] | |
Nivolumab (with chemotherapy) | PD-1 | Oesophageal adenocarcinoma | NCT02872116 | Phase III | [172] | |
Pembrolizumab | PD-1 | Advanced Colorectal Cancer | NCT02563002 | Phase III | [173] | |
Balstilimab/Zalifrelimab | PD-1/ CTLA-4 | Advanced cervical cancer | NCT03495882 | Phase II | [174] | |
Tremelimumab | CTLA-4 | HCC | NCT01853618 | Phase I/II | [175] | |
LY3415244 | PD-L1/ TIM-3 | Advanced solid tumors | NCT03752177 | Phase I | [176] | |
Atezolizumab | PD-L1 | Non-squamous NSCLC | JapicCTI-184038 | Phase II | [177] | |
Pembrolizumab | PD-L1 | NSCLC | NCT02142738 | Phase III | [178] | |
Tiragolumab | PD-L1 | NSCLC | NCT03563716 | Phase III | [179] | |
Induced differentiation strategy | ATRA (with apatinib) | Differentiation | Head and neck adenoid cystic carcinoma | NCT02775370 | phase II | [180] |
ATRA | Differentiation | Adenoid cystic carcinoma | / | phase II | [181] | |
ATRA (with belinostat) | Differentiation | Pancreatic cancer | NCT03307148 | Phase I | [182] | |
ATRA (with paclitaxel and interferon α2b) | Differentiation | Cervical cancer | / | phase II | [183] | |
IDH1-vac | IDH1 | Newly diagnosed glioma | NCT02454634 | phase I | [184] | |
Olutasidenib (FT-2102) | IDH1 | Relapsed or refractory IDH1-mutant glioma | NCT03684811 | Phase Ib/II | [185] | |
Ivosidenib | IDH1 | Chemotherapy-refractory cholangiocarcinoma | NCT02989857 | phase III | [186] | |
Vorasidenib | IDH1/2 | Recurrent or progressive glioma | NCT02481154 | Phase I | [187] | |
Temozolomide | IDH1/2 | 1p/19q non-co-deleted anaplastic glioma | NCT00626990 | phase III | [188] | |
Olaparib | IDH1/2 | IDH1/IDH2-Mutant Mesenchymal Sarcomas | NCT02576444 | phase II | [189] |