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Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)

  • Authors:
    • Hiroshi Kobayashi
    • Shogo Imanaka
    • Hiroshi Shigetomi
  • View Affiliations

  • Published online on: January 11, 2022     https://doi.org/10.3892/ol.2022.13200
  • Article Number: 80
  • Copyright: © Kobayashi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recent advances in molecular genetics have expanded our understanding of ovarian cancer. High levels of reactive oxygen species (ROS) and upregulation of antioxidant genes are common characteristic features of human cancers. This review reconsiders novel therapeutic strategies for ovarian cancer by focusing on redox homeostasis. A literature search was performed for preclinical and clinical studies published between January 1998 and October 2021 in the PubMed database using a combination of specific terms. ROS serves a central role in tumor suppression and progression by inducing DNA damage and mutations, genomic instability, and aberrant anti‑ and pro‑tumorigenic signaling. Cancer cells increase their antioxidant capacity to neutralize the extra ROS. Additionally, antioxidants, such as CD44 variant isoform 9 (CD44v9) and nuclear factor erythroid 2‑related factor 2 (Nrf2), mediate redox homeostasis in ovarian cancer. Furthermore, studies conducted on different cancer types revealed the dual role of antioxidants in tumor progression and inhibition. However, in animal models, genetic loss of antioxidant capacity in the host cannot block cancer initiation and progression. Host‑derived antioxidant systems are essential to suppress carcinogenesis, suggesting that antioxidants serve a pivotal role in suppressing cancer development. By contrast, antioxidant activation in cancer cells confers aggressive phenotypes. Antioxidant inhibitors can promote cancer cell death by enhancing ROS levels. Concurrent inhibition of CD44v9 and Nrf2 may trigger apoptosis induction, potentiate chemosensitivity and enhance antitumor activities through the ROS‑activated p38/p21 pathway. Antioxidants may have tumor‑promoting and ‑suppressive functions. Therefore, an improved understanding of the role of antioxidants in redox homeostasis and developing antioxidant‑specific inhibitors is necessary for treating ovarian cancer.
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March-2022
Volume 23 Issue 3

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Spandidos Publications style
Kobayashi H, Imanaka S and Shigetomi H: Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review). Oncol Lett 23: 80, 2022
APA
Kobayashi, H., Imanaka, S., & Shigetomi, H. (2022). Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review). Oncology Letters, 23, 80. https://doi.org/10.3892/ol.2022.13200
MLA
Kobayashi, H., Imanaka, S., Shigetomi, H."Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)". Oncology Letters 23.3 (2022): 80.
Chicago
Kobayashi, H., Imanaka, S., Shigetomi, H."Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis (Review)". Oncology Letters 23, no. 3 (2022): 80. https://doi.org/10.3892/ol.2022.13200