Table 1.
Preclinical studies of therapeutic compounds directed against breast cancer stem-like cells.
| Therapeutic Molecule | Targeting | Effects | Ref |
|---|---|---|---|
| LPT-HA-NCs | CD44 | Anticancer activity and delays tumor growth | [63] |
| Hyaluronan-conjugated liposomes encapsulating gemcitabine | CD44 | Inhibits migration and colony formation ability in vitro assays. Potent antitumor effect in vivo | [64] |
| Polymeric micelles functionalized with anti-CD44 antibodies and loaded with paclitaxel | CD44 | Increases the sensitivity of mammary CSCs to PTX treatment | [66] |
| FKBPL and its peptide derivatives | CD44 | It inhibits tumor growth and CD44-dependent antiangiogenic activity. It also targeting CD44-positive BCSCs, it also inhibits migration, invasion, and formation of mammospheres resistant to endocrine therapy. It reduces lung metastases in an in vivo model by downregulating DLL4 and Notch4 | [109,110] |
| Fusion protein dCD133KDEL | CD133 | Selectively inhibits CD133+ ductal breast carcinoma cells, causing regression of tumor growth in mice | [71] |
| Polymeric nanoparticles conjugated with an anti-CD133 antibody loaded with paclitaxel | CD133 | Reduces the number of mammospheres and cell colonies. In animal models decreases tumor volume | [72] |
| 3WJ/CD133apt/anti-miR21 nanoparticles | CD133 | High specificity in targeting TNBC tumor. High efficacy in tumor growth inhibition | [73] |
| Catumaxomab | EpCAM | Eliminates chemoresistant EpCAM-positive triple-negative cell lines | [78] |
| EpCAM aptamer-linked small-interfering RNA chimeras | EpCAM | Delays tumor growth and improves function of tumor-infiltrating immune cells | [79] |
| B6H12 | CD47 | Inhibits proliferation, asymmetric division, and KLF4 expression in BCSC | [81] |
| B6H12.2 | CD47 and HER2 | Inhibits the phagocytosis capacity of macrophages and abolishes the aggressive BCSCs phenotype of BCSCs | [82] |
| Metformin in Herceptin-Conjugated Liposome | HER2 | Inhibits proliferation and migration of BCSCs in vitro. In an animal model, reduces tumor mass and extends tumor remission | [85] |
| Carbon-ion beam combined with lapatinib | HER2 | Decreases BCSC ratio, cell viability, spheroid formation, and promotes apoptosis | [86] |
| CWP232228 | Wnt/β- catenin pathway | Inhibits sphere formation, decreases the proportion of BCSCs resistant to conventional therapy, and further reduces tumor growth and metastasis in vivo | [100] |
| EW-7197 | TGF-β signaling pathway inhibitor | In combination with PTX reduces the EMT process and proportion of BCSCs | [102] |
| LY2157299 | TGF-β signaling pathway inhibitor | Reduces the population of BCSCs resistant to PTX and abolishes the tumor-initiating potential of BCSCs after chemotherapy | [103] |
| Napabucasin | STAT3 inhibitor | Attenuates the BC cell resistance to tamoxifen by reducing the BCSC population | [91] |
| DAPT, GDC-0449, Salinomycin, Ruxolitinib, and Stattic | Notch, Hedgehog, Wnt/β-catenin, JAK, and JAK/STAT3, respectively | Antiproliferative and proapoptotic activities, suppress invasion and self-renewal of BCSC in vitro. They suppress the ability to form tumors in vivo | [15] |
| GANT61 | Non-canonical hedgehog pathway | Decreases E2-induced GLI1/2 activation and the proportion of BCSCs in ER-positive BC and TNBC cells | [89,114] |
| Disulfiram | STAT3 pathway | Inhibits STAT3 pathway suppressing stem properties in BC | [125,127] |
| Salinomycin | WNT and Hh signaling pathways | Reduces the proportion of BCSC and inhibits mammary tumor growth | [134] |
| Pyrvinium pamoate | Selective WNT pathway inhibitor | Inhibits proliferation and self-renewal of CSCs in BC cell lines. In the xenograft model of BC, strongly delays tumor development | [136] |
| Pranlukast | CD49f | Reduces the CSC population in TNBC cells | [138] |
| Benztropine Mesylate | NS | Decreases cell subpopulation with ALDH1 activity and CD44+/CD24− phenotype, diminishes mammosphere formation, and BCSC self-renewal capacities | [137] |
BC: breast cancer; BCSC: breast cancer stem cell; TNBC: triple-negative breast cancer; GLI: glioma-associated oncogene; PTX: Paclitaxel; HER2: Human epidermal growth factor receptor 2; GSI: γ-secretase inhibitor; NS: not specified.