• Open Access

Unfolded protein response to autophagy as a promising druggable target for anticancer therapy

Authors

  • Dong Hoon Suh,

    1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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  • Mi-Kyung Kim,

    1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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  • Hee Seung Kim,

    1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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  • Hyun Hoon Chung,

    1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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  • Yong Sang Song

    1. Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea.
    2. Cancer Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
    3. Department of Agricultural Biotechnology, Seoul National University, Seoul, Republic of Korea
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Yong Sang Song, M.D., Ph.D., Department of Obstetrics and Gynecology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea. yssong@snu.ac.kr

Abstract

The endoplasmic reticulum (ER) is responsible for protein processing. In rapidly proliferating tumor cells, the ER tends to be overloaded with unfolded and misfolded proteins due to high metabolic demand. With the limited protein-folding capacity of the ER, tumor cells often suffer from more ER stress than do normal cells. Thus, cellular stress responses to cope with ER stress, such as the unfolded protein response (UPR) and autophagy, might be more activated in cancer cells than in normal cells. The complex signaling pathways from the UPR to autophagy provide promising druggable targets; a number of UPR/autophagy-targeted anticancer agents are currently in development in preclinical and clinical studies. In this short review we will discuss the potential anticancer efficacy of modulators of cellular stress responses, especially UPR and autophagy, on the basis of their signaling pathways. In addition, the current developmental status of the UPR/autophagy-targeted agents will be discussed.

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