Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review
Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal dis...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/8/1896 |
| _version_ | 1797558328799264768 |
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| author | Kevin Dzobo Dimakatso Alice Senthebane Chelene Ganz Nicholas Ekow Thomford Ambroise Wonkam Collet Dandara |
| author_facet | Kevin Dzobo Dimakatso Alice Senthebane Chelene Ganz Nicholas Ekow Thomford Ambroise Wonkam Collet Dandara |
| author_sort | Kevin Dzobo |
| collection | DOAJ |
| description | Despite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis. |
| first_indexed | 2024-03-10T17:29:57Z |
| format | Article |
| id | doaj.art-ad4bb9a79a184371bdd2146020f56ada |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T17:29:57Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ad4bb9a79a184371bdd2146020f56ada2023-11-20T10:04:21ZengMDPI AGCells2073-44092020-08-0198189610.3390/cells9081896Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated ReviewKevin Dzobo0Dimakatso Alice Senthebane1Chelene Ganz2Nicholas Ekow Thomford3Ambroise Wonkam4Collet Dandara5International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South AfricaInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South AfricaInternational Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Wernher and Beit Building (South), UCT Medical Campus, Anzio Road, Observatory, Cape Town 7925, South AfricaDivision of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaDivision of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaDivision of Human Genetics, Department of Pathology and Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town 7925, South AfricaDespite great strides being achieved in improving cancer patients’ outcomes through better therapies and combinatorial treatment, several hurdles still remain due to therapy resistance, cancer recurrence and metastasis. Drug resistance culminating in relapse continues to be associated with fatal disease. The cancer stem cell theory posits that tumors are driven by specialized cancer cells called cancer stem cells (CSCs). CSCs are a subpopulation of cancer cells known to be resistant to therapy and cause metastasis. Whilst the debate on whether CSCs are the origins of the primary tumor rages on, CSCs have been further characterized in many cancers with data illustrating that CSCs display great abilities to self-renew, resist therapies due to enhanced epithelial to mesenchymal (EMT) properties, enhanced expression of ATP-binding cassette (ABC) membrane transporters, activation of several survival signaling pathways and increased immune evasion as well as DNA repair mechanisms. CSCs also display great heterogeneity with the consequential lack of specific CSC markers presenting a great challenge to their targeting. In this updated review we revisit CSCs within the tumor microenvironment (TME) and present novel treatment strategies targeting CSCs. These promising strategies include targeting CSCs-specific properties using small molecule inhibitors, immunotherapy, microRNA mediated inhibitors, epigenetic methods as well as targeting CSC niche-microenvironmental factors and differentiation. Lastly, we present recent clinical trials undertaken to try to turn the tide against cancer by targeting CSC-associated drug resistance and metastasis.https://www.mdpi.com/2073-4409/9/8/1896cancer stem cellstumor microenvironmentmetastasisdrug resistanceABC transportersepithelial to mesenchymal transition |
| spellingShingle | Kevin Dzobo Dimakatso Alice Senthebane Chelene Ganz Nicholas Ekow Thomford Ambroise Wonkam Collet Dandara Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review Cells cancer stem cells tumor microenvironment metastasis drug resistance ABC transporters epithelial to mesenchymal transition |
| title | Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review |
| title_full | Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review |
| title_fullStr | Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review |
| title_full_unstemmed | Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review |
| title_short | Advances in Therapeutic Targeting of Cancer Stem Cells within the Tumor Microenvironment: An Updated Review |
| title_sort | advances in therapeutic targeting of cancer stem cells within the tumor microenvironment an updated review |
| topic | cancer stem cells tumor microenvironment metastasis drug resistance ABC transporters epithelial to mesenchymal transition |
| url | https://www.mdpi.com/2073-4409/9/8/1896 |
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