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The mechanisms and reversal strategies of tumor radioresistance in esophageal squamous cell carcinoma

  • Review – Cancer Research
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Abstract

Esophageal squamous cell carcinoma (ESCC) is one of most lethal malignancies with high aggressive potential in the world. Radiotherapy is used as one curative treatment modality for ESCC patients. Due to radioresistance, the 5-year survival rates of patients after radiotherapy is less than 20%. Tumor radioresistance is very complex and heterogeneous. Cancer-associated fibroblasts (CAFs), as one major component of tumor microenvironment (TME), play critical roles in regulating tumor radioresponse through multiple mechanisms and are increasingly considered as important anti-cancer targets. Cancer stemness, which renders cancer cells to be extremely resistant to conventional therapies, is involved in ESCC radioresistance due to the activation of Wnt/β-catenin, Notch, Hedgehog and Hippo (HH) pathways, or the induction of epithelial–mesenchymal transition (EMT), hypoxia and autophagy. Non-protein-coding RNAs (ncRNAs), which account for more than 90% of the genome, are involved in esophageal cancer initiation and progression through regulating the activation or inactivation of downstream signaling pathways and the expressions of target genes. Herein, we mainly reviewed the role of CAFs, cancer stemness, non-coding RNAs as well as others in the development of radioresistance and clarify the involved mechanisms. Furthermore, we summarized the potential strategies which were reported to reverse radioresistance in ESCC. Together, this review gives a systematic coverage of radioresistance mechanisms and reversal strategies and contributes to better understanding of tumor radioresistance for the exploitation of novel intervention strategies in ESCC.

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Acknowledgements

This work was financially supported by National Natural Science Foundation of China (No. 81872477), Zhejiang Provincial Analysis and Test Scientific Research of China (No. 2018C37041) and Scientific Technology Research Foundation of Hangzhou City, Zhejiang Province, China (No. 20150733Q64).

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  1. Hongfang Zhang and Jingxing Si contributed equally to this manuscript.

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  1. Hangzhou Cancer Institution, Affiliated Hangzhou Cancer Hospital, Zhejiang University School of Medicine, Hangzhou, 310002, China

    Hongfang Zhang, Jing Yue & Shenglin Ma

  2. Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China

    Hongfang Zhang & Shenglin Ma

  3. Clinical Research Institute, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou, 310014, China

    Jingxing Si

  4. Zhejiang University Cancer Center, Hangzhou, 310058, China

    Shenglin Ma

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Zhang, H., Si, J., Yue, J. et al. The mechanisms and reversal strategies of tumor radioresistance in esophageal squamous cell carcinoma. J Cancer Res Clin Oncol 147, 1275–1286 (2021). https://doi.org/10.1007/s00432-020-03493-3

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