Table 1 Small-molecule compounds inhibiting CSC progression through suppressing Wnt signaling pathway
From: Emerging agents that target signaling pathways in cancer stem cells
Name | Target | Mechanism | Type of cancer | Phase | NCT number (starting time)/publication date | Assessment |
|---|---|---|---|---|---|---|
Wnt974 | Wnt | Inhibits the proliferation of breast CSCs | Breast cancer | Phase I | NCT01351103(May 10, 2011) | Dysgeusia [11] |
Niclosamide | Wnt/β-catenin | Selectively targets ovarian CSCs | Ovarian cancer | Preclinical | July, 2014 | |
LRP6, β-catenin | Decreases ALDH+ population cells | Basal-like breast cancer | Preclinical | April, 2014 | ||
Wnt/β-catenin | Suppresses CSC populations and self-renewal ability | Colorectal cancer | Phase II | NCT02519582 (August 11, 2015) | ||
ONC201 | Wnt/β-catenin | Inhibits CSC self-renewal and deregulates CSC markers and CSC-related gene expression | Glioblastoma cancer | Phase I/II | NCT02038699 (January 16, 2014) | Well tolerated, Grade III neutropenia, Grade II allergic [15, 16] |
Prostate cancer | Preclinical | August 2, 2017 | ||||
XAV939 | β-catenin | Attenuates CSC-mediated chemoresistance | Colon cancer | Preclinical | April, 2016 | Induces cardiotoxicity and limited therapeutic window [17] |
HNSCC | Preclinical | October, 2019 | ||||
TFP | Wnt/β-catenin | Inhibits lung CSC spheroid formation and suppresses lung CSC marker expression (such as CD44/CD133) | Lung cancer | Preclinical | December 1, 2012 | Induces little systemic toxicity, but grade 0–2 neurologic toxicity [18, 19] |
Chelerythrine | β-catenin | Inhibits CSCs invasion, spheroid-forming ability, and the stem marker such as SOX2 | NSCLC | Preclinical | January 6, 2020 | |
FH535 | Wnt/β-catenin | Deregulates pancreatic CSC marker CD24 and CD44 expression | Pancreatic cancer | Preclinical | July 26, 2016 | Without side effects according to the current studies, still need experiments to prove [22] |
Wnt-C59 | Wnt | Decreases sphere formation of CSCs | NPC | Preclinical | June 10, 2015 | Exhibits no apparent toxicity in mice; needs experiments to prove [23] |
IWR-1 | β-catenin | Impairs CSCs self-renewal and hampers the expression of key stem markers, and increases doxorubicin sensitivity | Osteosarcoma | Preclinical | February 1, 2018 | Well tolerated in mice, but still needs to be thoroughly studied [24] |
IC-2 | Wnt | Reduces the population of CD44+ (liver CSCs) and the ability of sphere-forming ability | HCC | Preclinical | July, 2017 | Not reported, still needs experiments to prove |
Wnt | Reduces the expression of CSC marker and sphere formation ability | CRC | Preclinical | August, 2017 | ||
JIB-04 | β-catenin | Inhibits the metastasis of colorectal CSCs | Colorectal cancer | Preclinical | April 26, 2018 | Without general toxicity in JIB-04-treated mice, but still needs experiments to prove [25] |
DTX and SFN | β-catenin | Inhibits the self-renewal ability of breast CSCs | Breast cancer | Preclinical | July, 2016 | DTX has the side effect of neurological toxicity, nausea, diarrhea, and alopecia, but SFN is without significant toxicity [26, 27] |
PP | β-catenin | Inhibits the self-renewal ability of breast CSCs | Breast cancer | Preclinical | March, 2016 | PP shows no obvious toxicity in mice. But the poor targeting of it made the dosage large. It would be better to improve dosage form and develop new derivatives [28] |
OXT-328 | October, 2012 | Safety according to the recent researches [28] | ||||
AD and Ts | Wnt/β-catenin | Decreases CSC number and activity, and reduces CSC marker expression (such as SOX2, ALDH1, and NOS2) | Lung cancer | Preclinical | December 3, 2019 | AD has hepatoxicity, and TS is without toxic side effects in nude mice [29, 30] |