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

Ahmed Y. Ali, Lee Farrand, Ji Young Kim, Sanguine Byun, Jeong Yong Suh, Hyong Joo Lee, Benjamin K. Tsang

Research output: Contribution to journalArticlepeer-review

73 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)58-67
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume1271
Issue number1
DOIs
Publication statusPublished - 2012 Oct

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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