Cancer Stem Cells and Targeting Strategies
Abstract
:1. Introduction
2. Cancer Stem Cells
3. Cancer Stemness, Therapy Resistance and Cancer Recurrence
3.1. Low Proliferation Rate
3.2. Expression of ATP-Binding Cassette (ABC) Transporters
3.3. Increased Expression of Aldehyde Dehydrogenases (ALDHs)
3.4. Resistance to Apoptosis
3.5. DNA Repair Response
4. CSC Microenvironment
4.1. Cancer-Associated Fibroblasts (CAFs)
4.2. Immune Cells
4.3. Mesenchymal Stem Cells (MSCs)
4.4. Endothelial Cells
5. Cancer Stemness, EMT and Tumour Progression
6. CSC Metabolism
7. Targeting Strategies of CSCs
7.1. Targeting Cell Surface Biomarkers of CSCs
7.1.1. CD133
7.1.2. CD44
7.1.3. EpCAM
7.1.4. CD47
7.2. Dendritic Cell-Based Vaccines
8. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
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Tumour | Biomarkers | References |
---|---|---|
Breast cancer | CD44+/CD24−/low/ALDH+ | [16] |
Prostate cancer | CD44+/a2b1+/ALDH+ | [34] |
Melanoma | ABCB5+ | [17] |
CD20+ | [18] | |
CD271+ | ||
Glioblastoma | CD133+ | [20] |
Colon cancer | CD133+/CD44+/ALDH+ | [21] |
EpCAM+/CD44+/CD166+ | [22] | |
CD44+/CD24+ | [23] | |
CD133+/CD24+ | [24] | |
Lung cancer | CD133+ | |
CD44+ | ||
ALDH+ | [35,47] | |
CD117+ | ||
Gastric cancer | CD133+ | |
CD44+/CD24+ | [25] | |
CD90+ | [26] | |
CD44+/CD54+ | ||
Head and neck cancer | CD44+/ALDH+ | [27] |
CD44+/CD66- | ||
Ovarian cancer | CD133+ | [28] |
CD44+ | ||
ALDH+ | ||
CD117+ | ||
Pancreatic cancer | CD133+/CD44+/CD24+/ESA+ | [29] |
Liver cancer | CD133+/CD44+ | [30] |
CD90+ | [31] | |
EpCAM+ | [32] | |
CD13+ | [33] |
Target | Tumour Type | Therapy | Clinical Trial/Reports | Results |
---|---|---|---|---|
CD133 | Advanced cholangiosarcoma | Cocktail CD133 CAR-T and CART-EGFR | NCT02541370 (Phase I and II) | Toxicity |
Glioblastoma multiforme | ICT-121 DC vaccine | NCT02049489 (Phase I) | Not published | |
CD44 | Refractory Acute Myeloid Leukemia | Monoclonal antibody (RG7356) | 146 | Limited clinical activity |
EpCAM | Metastatic colorectal cancer | Edrecolomab (Monoclonal antibody) | 151 | Limited response |
150 | Not statistically significant | |||
3622W94 (Monoclonal antibody) | 152 | Toxicity | ||
ING-1 (Monoclonal antibody) | Toxicity | |||
Adecatumumab (Monoclonal antibody) | 153 | Favourable response in patients with highest expression | ||
Various types of tumours | EPCAM-targeted CAR-T cells | NCT02729493 (N/A) | Ongoing | |
NCT02725125 (N/A) | Ongoing | |||
NCT02915445 (Phase I) | Ongoing | |||
NCT03013712 (Phase I and II) | Ongoing | |||
CD47 | Various solid tumours and hematological malignancies | Hu5F9-G4 (Monoclonal antibody) | NCT02216409 (Phase I) | Not statistically significant |
NCT02678338 (Phase I) | Not published | |||
Combination Hu5F9-G4 and Cetuximab | NCT02953782 (Phase I and II) | Ongoing | ||
Combination Hu5F9-G4 and Retuximab | NCT02953509 (Phase I and II) | Ongoing | ||
CC-90002 (Monoclonal antibody) | NCT02641002 (Phase I) | Ongoing | ||
Combination CC-90002 and Retuximab | NCT02367196 (Phase I) | Ongoing | ||
Autogenic glioma stem-like cells (A2B5+) | Glioblastoma multiforme | Dendritic cell-based vaccine | NCT01567202 (Phase II) | Ongoing |
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Barbato, L.; Bocchetti, M.; Di Biase, A.; Regad, T. Cancer Stem Cells and Targeting Strategies. Cells 2019, 8, 926. https://doi.org/10.3390/cells8080926
Barbato L, Bocchetti M, Di Biase A, Regad T. Cancer Stem Cells and Targeting Strategies. Cells. 2019; 8(8):926. https://doi.org/10.3390/cells8080926
Chicago/Turabian StyleBarbato, Luisa, Marco Bocchetti, Anna Di Biase, and Tarik Regad. 2019. "Cancer Stem Cells and Targeting Strategies" Cells 8, no. 8: 926. https://doi.org/10.3390/cells8080926