CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer
Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% of all cancer patients either alone or in combination with other treatment modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances in RT,...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-07-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/7/1651 |
| _version_ | 1797562840560697344 |
|---|---|
| author | María Auxiliadora Olivares-Urbano Carmen Griñán-Lisón Juan Antonio Marchal María Isabel Núñez |
| author_facet | María Auxiliadora Olivares-Urbano Carmen Griñán-Lisón Juan Antonio Marchal María Isabel Núñez |
| author_sort | María Auxiliadora Olivares-Urbano |
| collection | DOAJ |
| description | Radiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% of all cancer patients either alone or in combination with other treatment modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances in RT, which allow a more precise delivery of radiation while progressively minimizing the impact on normal tissues, issues like radioresistance and tumor recurrence remain important challenges. Tumor heterogeneity is responsible for the variation in the radiation response of the different tumor subpopulations. A main factor related to radioresistance is the presence of cancer stem cells (CSC) inside tumors, which are responsible for metastases, relapses, RT failure, and a poor prognosis in cancer patients. The plasticity of CSCs, a process highly dependent on the epithelial–mesenchymal transition (EMT) and associated to cell dedifferentiation, complicates the identification and eradication of CSCs and it might be involved in disease relapse and progression after irradiation. The tumor microenvironment and the interactions of CSCs with their niches also play an important role in the response to RT. This review provides a deep insight into the characteristics and radioresistance mechanisms of CSCs and into the role of CSCs and tumor microenvironment in both the primary tumor and metastasis in response to radiation, and the radiobiological principles related to the CSC response to RT. Finally, we summarize the major advances and clinical trials on the development of CSC-based therapies combined with RT to overcome radioresistance. A better understanding of the potential therapeutic targets for CSC radiosensitization will provide safer and more efficient combination strategies, which in turn will improve the live expectancy and curability of cancer patients. |
| first_indexed | 2024-03-10T18:34:29Z |
| format | Article |
| id | doaj.art-660b9aae10e04172bbbcfda011af8759 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T18:34:29Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-660b9aae10e04172bbbcfda011af87592023-11-20T06:19:26ZengMDPI AGCells2073-44092020-07-0197165110.3390/cells9071651CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in CancerMaría Auxiliadora Olivares-Urbano0Carmen Griñán-Lisón1Juan Antonio Marchal2María Isabel Núñez3Department of Radiology and Physical Medicine, University of Granada, 18016 Granada, SpainBiopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, 18100 Granada, SpainBiopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, 18100 Granada, SpainDepartment of Radiology and Physical Medicine, University of Granada, 18016 Granada, SpainRadiotherapy (RT) is a modality of oncologic treatment that can be used to treat approximately 50% of all cancer patients either alone or in combination with other treatment modalities such as surgery, chemotherapy, immunotherapy, and therapeutic targeting. Despite the technological advances in RT, which allow a more precise delivery of radiation while progressively minimizing the impact on normal tissues, issues like radioresistance and tumor recurrence remain important challenges. Tumor heterogeneity is responsible for the variation in the radiation response of the different tumor subpopulations. A main factor related to radioresistance is the presence of cancer stem cells (CSC) inside tumors, which are responsible for metastases, relapses, RT failure, and a poor prognosis in cancer patients. The plasticity of CSCs, a process highly dependent on the epithelial–mesenchymal transition (EMT) and associated to cell dedifferentiation, complicates the identification and eradication of CSCs and it might be involved in disease relapse and progression after irradiation. The tumor microenvironment and the interactions of CSCs with their niches also play an important role in the response to RT. This review provides a deep insight into the characteristics and radioresistance mechanisms of CSCs and into the role of CSCs and tumor microenvironment in both the primary tumor and metastasis in response to radiation, and the radiobiological principles related to the CSC response to RT. Finally, we summarize the major advances and clinical trials on the development of CSC-based therapies combined with RT to overcome radioresistance. A better understanding of the potential therapeutic targets for CSC radiosensitization will provide safer and more efficient combination strategies, which in turn will improve the live expectancy and curability of cancer patients.https://www.mdpi.com/2073-4409/9/7/1651radiation resistanceCSC intratumoral radiosensitivity heterogeneityaccelerated repopulationCSC nicheCSC metabolismsignaling pathways |
| spellingShingle | María Auxiliadora Olivares-Urbano Carmen Griñán-Lisón Juan Antonio Marchal María Isabel Núñez CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer Cells radiation resistance CSC intratumoral radiosensitivity heterogeneity accelerated repopulation CSC niche CSC metabolism signaling pathways |
| title | CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer |
| title_full | CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer |
| title_fullStr | CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer |
| title_full_unstemmed | CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer |
| title_short | CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer |
| title_sort | csc radioresistance a therapeutic challenge to improve radiotherapy effectiveness in cancer |
| topic | radiation resistance CSC intratumoral radiosensitivity heterogeneity accelerated repopulation CSC niche CSC metabolism signaling pathways |
| url | https://www.mdpi.com/2073-4409/9/7/1651 |
| work_keys_str_mv | AT mariaauxiliadoraolivaresurbano cscradioresistanceatherapeuticchallengetoimproveradiotherapyeffectivenessincancer AT carmengrinanlison cscradioresistanceatherapeuticchallengetoimproveradiotherapyeffectivenessincancer AT juanantoniomarchal cscradioresistanceatherapeuticchallengetoimproveradiotherapyeffectivenessincancer AT mariaisabelnunez cscradioresistanceatherapeuticchallengetoimproveradiotherapyeffectivenessincancer |