• Open Access

Molecular determinants of ovarian cancer chemoresistance: new insights into an old conundrum

Authors

  • Ahmed Y. Ali,

    1. Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    2. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
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  • Lee Farrand,

    1. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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  • Ji Young Kim,

    1. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
    2. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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  • Sanguine Byun,

    1. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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  • Jeong-Yong Suh,

    1. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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  • Hyong Joo Lee,

    1. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
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  • Benjamin K. Tsang

    1. Departments of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
    2. Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
    3. Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.
    4. Department of Obstetrics and Gynecology, University of Ottawa, Ottawa, Ontario, Canada
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Errata

This article is corrected by:

  1. Errata: Erratum for Ann. N.Y. Acad. Sci. 2012. 1271: 58–67 Volume 1299, 100, Article first published online: 24 September 2013

Benjamin K. Tsang, Ph.D., Ottawa Hospital Research Institute, 725 Parkdale Avenue, Ottawa, Ontario, Canada K1Y 4E9. btsang@ohri.ca7

Abstract

Ovarian cancer is the most lethal gynecological malignancy. Cisplatin and its derivatives are first-line chemotherapeutics, and their resistance is a major hurdle in successful ovarian cancer treatment. Understanding the molecular dysregulation underlying chemoresistance is important for enhancing therapeutic outcome. Here, we review two established pathways in cancer chemoresistance. p53 is a major tumor suppressor regulating proliferation and apoptosis, and its mutation is a frequent event in human malignancies. The PI3K/Akt axis is a key oncogenic pathway regulating survival and tumorigenesis by controlling several tumor suppressors, including p53. The interplay between these pathways is well established, although the oncogenic phosphatase PPM1D adds a new layer to this intricate relationship and provides new insights into the processes determining cell fate. Inhibition of the PI3K/Akt pathway by functional food compounds as an adjunct to chemotherapeutics may tip the balance in favor of apoptosis rather than survival, enhancing therapeutic efficacy, and reducing side effects.

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