Department of Radiology and Physical Medicine, University of Granada, 18016 Granada, Spain.
Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, 18100 Granada, Spain.
Cells. 2020 Jul 9;9(7):1651. doi: 10.3390/cells9071651.
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.
放射治疗（RT）是一种肿瘤治疗方式，可单独使用或与其他治疗方式（如手术、化疗、免疫疗法和靶向治疗）联合使用，治疗约 50%的癌症患者。尽管 RT 在技术上取得了进步，能够更精确地输送辐射，同时逐渐减少对正常组织的影响，但像放射性抵抗和肿瘤复发等问题仍然是重要的挑战。肿瘤异质性导致不同肿瘤亚群对辐射的反应存在差异。与放射性抵抗相关的一个主要因素是肿瘤内存在癌症干细胞（CSC），CSC 负责转移、复发、RT 失败和癌症患者预后不良。CSC 的可塑性，这一过程高度依赖于上皮-间充质转化（EMT）和相关的细胞去分化，使 CSC 的识别和根除变得复杂，并且可能与照射后疾病的复发和进展有关。肿瘤微环境和 CSC 与其龛之间的相互作用也在 RT 反应中发挥重要作用。本综述深入探讨了 CSC 的特征和放射性抵抗机制，以及 CSC 和肿瘤微环境在原发肿瘤和转移瘤对辐射反应中的作用，以及与 CSC 对 RT 反应相关的放射生物学原理。最后，我们总结了基于 CSC 的联合 RT 治疗克服放射性抵抗的主要进展和临床试验。更好地了解 CSC 放射增敏的潜在治疗靶点将提供更安全、更有效的联合策略，从而提高癌症患者的预期寿命和治愈率。
