CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy E ectiveness in Cancer
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Olivares Urbano, María Auxiliadora; Griñan-Lison, Carmen; Marchal Corrales, Juan Antonio; Núñez Torres, María IsabelEditorial
MDPI
Materia
radiation resistance CSC intratumoral radiosensitivity heterogeneity accelerated repopulation
Date
2020-07-09Referencia bibliográfica
Olivares Urbano, M.A. et. al. Cells 2020, 9, 1651. [https://doi.org/10.3390/cells9071651]
Sponsorship
Ministerio de Ciencia, Innovación y Universidades (MICIU, project noº RTI2018-101309-B-C2, FEDER Funds); Instituto de Salud Carlos III (PIE16-00045 and DTS19/00145); Consejería de Economía, Conocimiento, Empresas y Universidad de la Junta de Andalucía and European Regional Development Fund (ERDF), ref. SOMM17/6109/UGR (UCE-PP2017-3); Chair “Doctors Galera-Requena in cancer stem cell research” (CMC-CTS963)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 di erent 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 dedi erentiation, 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 e cient combination strategies, which in turn will improve the live expectancy and curability
of cancer patients.