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Targeting paraptosis in cancer: opportunities and challenges

Cancer Gene Therapy volume 31, pages 349–363 (2024)Cite this article

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Abstract

Cell death can be classified into two primary categories: accidental cell death and regulated cell death (RCD). Within RCD, there are distinct apoptotic and non-apoptotic cell death pathways. Among the various forms of non-apoptotic RCD, paraptosis stands out as a unique mechanism characterized by distinct morphological changes within cells. These alterations encompass cytoplasmic vacuolization, organelle swelling, notably in the endoplasmic reticulum and mitochondria, and the absence of typical apoptotic features, such as cell shrinkage and DNA fragmentation. Biochemically, paraptosis distinguishes itself by its independence from caspases, which are conventionally associated with apoptotic death. This intriguing cell death pathway can be initiated by various cellular stressors, including oxidative stress, protein misfolding, and specific chemical compounds. Dysregulated paraptosis plays a pivotal role in several critical cancer-related processes, such as autophagic degradation, drug resistance, and angiogenesis. This review provides a comprehensive overview of recent advancements in our understanding of the mechanisms and regulation of paraptosis. Additionally, it delves into the potential of paraptosis-related compounds for targeted cancer treatment, with the aim of enhancing treatment efficacy while minimizing harm to healthy cells.

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Fig. 1: Core molecular machinery and signaling regulation of paraptosis.
Fig. 2: Paraptosis in tumor biology.
Fig. 3: Paraptosis in targeted therapy.

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Acknowledgements

JL was supported by the NSFC grants (3220055594 and 82372152).

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Author notes

  1. These authors contributed equally: Fangquan Chen, Hu Tang.

Authors and Affiliations

  1. DAMP Laboratory, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510150, China

    Fangquan Chen, Hu Tang, Xiutao Cai, Junhao Lin, Limin Xiang & Jiao Liu

  2. Department of Surgery, UT Southwestern Medical Center, Dallas, TX, 75390, USA

    Rui Kang & Daolin Tang

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  1. Fangquan Chen
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  2. Hu Tang
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  3. Xiutao Cai
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  4. Junhao Lin
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  5. Limin Xiang
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  6. Rui Kang
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  7. Jiao Liu
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  8. Daolin Tang
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FC, HT and DT wrote the manuscript. RK and JL edited the manuscript. All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.

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Correspondence to Jiao Liu or Daolin Tang.

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DT is an editorial board member of Cancer Gene Therapy. The authors declare no other conflicts of interest or financial interests.

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Chen, F., Tang, H., Cai, X. et al. Targeting paraptosis in cancer: opportunities and challenges. Cancer Gene Ther 31, 349–363 (2024). https://doi.org/10.1038/s41417-023-00722-y

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  • DOI: https://doi.org/10.1038/s41417-023-00722-y

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