Publication:
CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer.

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Date

2020-07-09

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Olivares-Urbano, Maria Auxiliadora
Griñan-Lison, Carmen
Marchal, Juan Antonio
Nuñez, Maria Isabel

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MDPI AG
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Abstract

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.

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Animals
Humans
Neoplasms
Neoplastic Stem Cells
Radiation Tolerance
Radiotherapy
Instituto de Salud Carlos III Spanish Government

DeCS Terms

Neoplasias
Radiación
Recurrencia
Metástasis de la Neoplasia
Microambiente Tumoral
Células Madre Neoplásicas
Radioterapia
Desdiferenciación celular
Inmunoterapia

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Keywords

CSC intratumoral radiosensitivity heterogeneity, CSC metabolism, CSC niche, accelerated repopulation, radiation resistance, signaling pathways, tumor microenvironment

Citation

Olivares-Urbano MA, Griñán-Lisón C, Marchal JA, Núñez MI. CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer. Cells. 2020 Jul 9;9(7):1651.