Table 2.
List of BCSC-targeted strategies used in clinical trials.
| Strategy | Target | Drug | Phase | Status | Stage/Type | Identifier | Reference |
|---|---|---|---|---|---|---|---|
| Notch signaling | γ-Secretase | MK-0752 | Pilot-study | Unknown | Early stage BC | NCT00756717 | [82] |
| I/II | Completed | Advanced or metastatic | NCT00645333 | [24] | |||
| I | Completed | Metastatic or advanced | NCT00106145 | [73] | |||
| PF-03084014 (Nirogacestat) | I | Completed | Advanced | NCT01876251 | [83] | ||
| II | Completed | Advanced | NCT02299635 | [84] | |||
| LY3039478 (Crenigacestat) | I | Recruiting | Advanced or metastatic | NCT02784795 | [85] | ||
| RO4929097 (RG-4733) | I | Completed | Advanced | NCT01208441 | [82] | ||
| I | Completed | Advanced | NCT01238133 | [86] | |||
| I | Completed | Metastatic | NCT01071564 | [76] | |||
| I | Completed | Advanced or metastatic | NCT01149356 | [86] | |||
| II | Completed | Advanced, metastatic or recurrent | NCT01151449 | [82] | |||
| I | Completed | Refractory | NCT01158274 | [82] | |||
| I | Completed | Advanced | NCT01131234 | [87] | |||
| Protein-protein interaction | CB-103 | I/II | Recruiting | Advanced or metastatic | NCT03422679 | [88] | |
| Hedgehog signaling | Hedgehog/PTCH1 | GDC-0449 (vismodegib) | II | Recruiting | TNBC | NCT02694224 | [88] |
| LDE225 (sonidegib) | I | Unknown | Advanced | NCT02027376 | [88] | ||
| I | Completed | Metastatic | NCT01576666 | [89] | |||
| HDAC signaling | HDAC | Vorinostat | I/II | Terminated | Advanced | NCT01118975 | [90] |
| HER2 signaling | HER2 | Lapatinib Ditosylate | II | Recruiting | Advanced or metastatic | NCT01868503 | - |
| Lapatinib | II | Ongoing, not recruiting | Advanced or metastatic | NCT00524303 | [25] | ||
| TGF-βIR signaling | Clusterin | Anti-clusterin mAb AB-16B5 | I | Completed | Advanced | NCT02412462 | [91] |
| TGF-βIR | Galunisertib/LY2157299 | II | Completed | Metastatic | NCT02538471 | [92] | |
| PI3K/Akt signaling | mTOR | Everolimus (RAD001) | III | Completed | Advanced | NCT00863655 | [93] |
| Akt | MK2206 | I | Ongoing, not recruiting | Advanced | NCT01281163 | [94] | |
| Ephrin signaling | EFNA4 | PF-06647263 | I | Completed | Advanced | NCT02078752 | [95] |
| VEGF signaling | HSP90 | Ganetespib | I | Completed | Metastatic HER2+ | NCT02060253 | [96] |
| CXCR signaling | CXCR | Reparixin | II | Recruiting | Metastatic | NCT01861054 | [97] |
| CXCR | Reparixin | I | Ongoing, not recruiting | Metastatic | NCT02001974 | [73] | |
| Wnt signaling | PORCN | LGK-974 (WNT974) | I | Recruiting | TNBC | NCT01351103 | [98] |
| Wnt-5a mimic | Foxy-5 | I | Completed | Metastatic | NCT02020291 | [99] | |
| Recruiting | Metastatic | NCT02655952 | [100] | ||||
| FZD receptors | OMP-18R5 (ventictumab) | I | Completed | Metastatic | NCT01973309 | [101] | |
| ROR1 | UC-961 (Cirmtuzumab) | I | Not recruiting | Metastatic | NCT02776917 | - | |
| Immunomodulation | CSC | CSC whole | I/II | Completed | Advanced | NCT02063893 | [26] |
| Mammoglobin-A | Vaccination with a pasmid DNA encoding mammaglobin-A | I | Completed | Metastatic | NCT00807781 | [102] | |
| Vaccination with a plasmid DNA encoding mammaglobin-A | I | Recruiting | Advanced | NCT02204098 | [103] | ||
| CYP1B1 | Vaccination with a plasmid DNA encoding CYP1B1 encapsulated in biodegradable microparticles | I | Completed | Advanced | NCT00381173 | - | |
| Multiple antigens | Plasmid-based vaccination strategy targeting multiple antigens of cancer stem cells | I | Recruiting | Advanced | NCT02157051 | - | |
| IGFBP2, HER2 and IGF1R | Vaccination with a plasmid encoding IGFBP2, HER2 and IGF1R | I | Recruiting | Advanced | NCT02780401 | - | |
| HER2 | Vaccination with a plasmid DNA encoding HER2 | I | Ongoing | Advanced | NCT00436254 | - | |
| Polypitopes DNA | Personalized polyepitope DNA vaccine | I | Recruiting | Advanced | NCT02348320 | - | |
| RNA vaccines | Immunogenic RNA vaccines | I | Recruiting | Advanced | NCT02316457 | - | |
| HER peptide (NeuVax) | Vaccination with a HER2-targeted peptide (NeuVax) | III | Ongoing | Advanced | NCT01479244 | ||
| Peptide (GP2 and AE37) | Vaccination with a HER2-targeted peptide (GP2 and AE37) | II | Ongoing | Advanced | NCT00524277 | [104] | |
| Synthetic long peptide | Vaccination with personalized synthetic long peptide vaccine | I | Recruiting | Advanced | NCT02427581 | - | |
| Alpha peptide | Vaccination with folate receptor alpha peptide vaccine | I | Recruiting | Advanced | NCT02593227 | - | |
| Peptides tumor-associated | Vaccination with four tumor-associated peptides | I | Recruiting | Rdvanced | NCT02826434 | - | |
| GM-CSF | Vaccination with autologous or allogeneic breast cancer cells engineered to secrete GM-CSF | I | Ongoing | Metastatic | NCT00399529 NCT00317603 | - | |
| TP53 | Anti-TP53 TCR-gene engineered lymphocytes and autologous dendritic cell-adenovirus TP53 vaccine | I | Completed | Metastatic | NCT00704938 | - | |
| Recombinant fusion protein of IL-2 linked to a single-chain TCR domain targeting TP53 | I | Completed | Metastatic | NCT00496860 | - | ||
| Tumor antigen | Immunotherapy with modified TCR targeting CEA tumor antigen | I | Ongoing, recruiting | Metastatic | NCT01022138 NCT02349724 | [105] | |
| Mesothelin | CAR-T cells targeting mesothelin | I | Recruiting | Advanced | NCT0258074 NCT02792114 | - | |
| CD133 | CAR-T cells targeting CD133 | I | Recruiting | Advanced | NCT02541370 | - | |
| EpCAM | CAR-T cells targeting EpCAM | I | Recruiting | Recurrent | NCT02915445 | - | |
| ROR1 | CAR-T cells targeting ROR1 | I | Recruiting | Recurrent | NCT02706392 | [106] | |
| MUC-1 | CAR-T cells targeting MUC-1 | I/II | Recruiting | Advanced | NCT02587689 | - | |
| HER2 | CAR-T cells targeting HER2 | I/II | Recruiting | Recurrent | NCT02547961 NCT02713984 | - | |
| MET | CAR-T cells targeting MET proto-oncogene | I/II | Ongoing | Advanced | NCT01837602 | [107] | |
| TP53 | Vaccination with adenovirus-TP53 trasduced DCs | I/II | Ongoing | Recurrent and advanced | NCT01042535 | [108] | |
| HER2 | Vaccination with adenovirus-HER2- trasduced DCs | I | Completed | Advanced | NCT00197522 NCT01730118 | - | |
| Cyclin B1/WT-1/CEF | Vaccination cyclin B1/WT-1/CEF pool-loaded DCs | I | Recruiting | Advanced | NCT02018458 | - | |
| Onco-peptides | Vaccination with autologous DCs pulsed with onco-peptides | I | Completed | Metastatic | NCT00197925 | - | |
| Tumor blood vessel antigen -derived peptides | Vaccination with DCs incorporating tumor blood vessel antigen-derived peptides | I | Recruiting | Metastatic | NCT02479230 | - | |
| Frizzled (Fzd) receptor | Vantictumab/OMP-18R5 Anti-Frizzled receptors mAb | Ib | Completed | Metastatic | NCT01973309 | - | |
| Gene-targeting | RRM2 | CALAA-01 (transferin-targeted cyclodextrin-containing polymer carrying siRNA against RRM2 | I | Completed | Advanced | NCT00689065 | [109,110] |
| Protein kinase N3 gene | Lipoplexed Atu-027 (AtuPLEX) | I | Recruiting | Advanced | NCT00938574 | [111] | |
| MiR-34a | MRX34 liposomal miR-34a mimic | I | Completed | Advanced | NCT01829971 | [112] | |
| Clusterin | OGX01 antisense oligonucleotide | II | Completed | Metastatic | NCT01578655 | [113] |