Table 3 Small-molecule compounds inhibiting CSC progression through suppressing Hh signalling 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 |
|---|---|---|---|---|---|---|
Glasdegib | Hh | Attenuates the potential of leukemia-initiation and increases the sensitivity of LSCs to chemotherapy | Leukemia | Approved | November 21, 2018 | Induces common side effect of chemotherapy drugs such as fatigue, nausea, and febrile neutropenia, but also has embryo-fetal toxicity [73] |
Sonidegib | SMO | Downregulates the expression of CSC markers and increases the sensitivity to paclitaxel | Breast cancer | Phase I | NCT02027376 (January 6, 2014) | Induces myalgia, fatigue, and abnormal hepatic function, and gastrointestinal toxicity and alopecia are related to the dose of Sonidegib [74, 75] |
Vismodegib | SMO | Inhibits BCSC self-renewal and mammosphere formation | Breast cancer | Phase II | NCT02694224 (February 29, 2016) | DLT, hyperbilirubinemia [76] |
Suppresses pancreatic CSC proliferation and survival | Pancreatic cancer | Phase II | NCT01064622(February 8, 2010) | |||
Decreases the stem markers (such as CD44 and ALDH) of colon CSCs | Colorectal cancer | Phase II | NCT00636610(March 14, 2008) | |||
Ciclesonide | Hh | Inhibits the growth of lung CSCs | Lung cancer | Preclinical | February 4, 2020 | Well tolerated, but as corticosteroid, it may inhibit bone growth [77] |
Cyclopamine | SMO | Inhibits bladder CSC self-renewal | Bladder cancer | Preclinical | March 1, 2016 | Induces holoprosencephaly, dystonia, and lethargy in rodents [78] |
GANT61 | GLI1 and GLI2 | Decreases the CSC population | Breast cancer | Preclinical | May, 2017 | No side effects in the mice according to the current studies [79] |