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Clinical application of ceramide in cancer treatment

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Abstract

Development of innovative strategies for cancer treatment is a pressing public health issue. Despite recent advances, the mechanisms of cancer progression and the resistance to cancer treatment have not been fully elucidated. Sphingolipids, including ceramide and sphingoshin-1-phosphate, are bioactive mediators that regulate cancer cell death and survival through the dynamic balance of what has been termed the ‘sphingolipid rheostat’. Specifically, ceramide, which acts as the central hub of sphingolipid metabolism, is generated via three major pathways by many stressors, including anti-cancer treatments, environmental stresses, and cytokines. We have previously shown in breast cancer patients that elevated ceramide correlated with less aggressive cancer phenotypes, leading to a prognostic impact. Recent studies showed that ceramide have the possibility of becoming the reinforcing agent of cancer treatment as well as other roles such as nanoparticles and diagnostic biomarker. We review ceramide as one of the key molecules to investigate in overcoming resistance to current drug therapies and in becoming one of the newest cancer treatments.

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Scientific Research Grant Number 18K19576 for MN, and 16K15610 for TW. MN was supported by the Uehara Memorial Foundation, Takeda Science Foundation, and Tsukada Medical Foundation. KT was supported by NIH/NCI grant R01CA160688 and Susan G. Komen Investigator Initiated Research Grant IIR12222224.

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Authors and Affiliations

  1. Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan

    Kazuki Moro, Masayuki Nagahashi, Kazuaki Takabe & Toshifumi Wakai

  2. Department of Surgery, Mayo Clinic, Jacksonville, FL, USA

    Emmanuel Gabriel

  3. Division of Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA

    Kazuaki Takabe

  4. Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York, Buffalo, NY, USA

    Kazuaki Takabe

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  1. Kazuki Moro
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Correspondence to Masayuki Nagahashi.

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Moro, K., Nagahashi, M., Gabriel, E. et al. Clinical application of ceramide in cancer treatment. Breast Cancer 26, 407–415 (2019). https://doi.org/10.1007/s12282-019-00953-8

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