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The roles of the COX2/PGE2/EP axis in therapeutic resistance

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Abstract

Therapeutic resistance has been and remains to be the major challenge in developing successful treatments for different cancers and therefore, understanding the underlying mechanisms in the development of therapeutic resistance is crucial in combating cancers. Multiple mechanisms underlie the development of therapeutic resistance, and the signaling pathways involved in cancer stem cell repopulation, enhanced epithelial-mesenchymal transition (EMT), inflammatory infiltration, and immunosuppression play pivotal roles in this process. Accumulating evidence indicates that the COX2/PGE2/EP axis plays crucial roles not only in tumor development including initiation and progression but also in the development of therapeutic resistance. In this review, we will first dissect the relationship between the COX2/PGE2/EP axis and therapeutic resistance by focusing on the roles of the COX2/PGE2/EP axis in cancer stem cell repopulation, EMT, and anti-cancer immunity. Then, we will summarize the currently available compounds/drugs targeting each component of this axis as well as some of the underlying mechanisms. We hope that better understanding the underlying mechanisms of the functional compounds will be helpful in seeking additive and/or synergistic effects against therapeutic resistance without or with minimal adverse consequence.

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Acknowledgements

This work was supported for Jun Jiang by the National Natural Science Foundation of China (NSFC) (Grant Nos.: 81772704 and 81172442) and Army Healthcare Foundation of China (Grant No.: 17BJZ13) and Dali Tong by NSFC (Grant No.: 81402120).

Author information

Authors and Affiliations

  1. Department of Urology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10#, Changjiang Zhilu, Yuzhong District, Chongqing, 400042, People’s Republic of China

    Dali Tong, Qiuli Liu, Lin-ang Wang, Qiubo Xie, Jian Pang, Yiqiang Huang, Luofu Wang, Gaolei Liu, Weihua Lan & Jun Jiang

  2. Department of Bio-Medical Sciences, Philadelphia College of Osteopathic Medicine, 4170 City Avenue, Philadelphia, PA, 19131, USA

    Dianzheng Zhang

Authors
  1. Dali Tong
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  2. Qiuli Liu
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  3. Lin-ang Wang
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  4. Qiubo Xie
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  5. Jian Pang
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  6. Yiqiang Huang
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  7. Luofu Wang
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  8. Gaolei Liu
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  9. Dianzheng Zhang
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  10. Weihua Lan
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  11. Jun Jiang
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Corresponding authors

Correspondence to Weihua Lan or Jun Jiang.

Additional information

Dali Tong and Qiuli Liu contribute equally to this review.

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Tong, D., Liu, Q., Wang, La. et al. The roles of the COX2/PGE2/EP axis in therapeutic resistance. Cancer Metastasis Rev 37, 355–368 (2018). https://doi.org/10.1007/s10555-018-9752-y

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  • DOI: https://doi.org/10.1007/s10555-018-9752-y

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