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Updated: Feb 11, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
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Mitotic Exit Dysfunction through the Deregulation of APC/C Characterizes Cisplatin-Resistant State in Epithelial

Anil Belur Nagaraj1, Olga Kovalenko2, Rita Avelar1

  • 1Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|April 15, 2018
PubMed

Insights

Cisplatin resistance in cancer cells involves a unique vulnerability in mitotic exit, dependent on Polo-like kinase 1 (PLK1). Targeting PLK1 offers a new strategy against resistant cancers, though PLK1 downregulation can cause resistance to therapies.

Area of Science:

  • Oncology
  • Cell Biology
  • Cancer Therapeutics

Background:

  • Acquired resistance to cisplatin is a significant challenge in cancer treatment.
  • Understanding the unique cellular mechanisms of resistant cancer cells is crucial for developing effective therapies.

Purpose of the Study:

  • To investigate mitotic exit mechanisms in cisplatin-resistant cancer cells.
  • To identify potential therapeutic targets for overcoming cisplatin resistance.

Main Methods:

  • Utilized cisplatin-resistant epithelial ovarian cancer (EOC) cell models.
  • Analyzed spindle checkpoint activity and Polo-like kinase 1 (PLK1) dependency.
  • Investigated the role of anaphase promoting complex/cyclosome (APC/C) dysfunction.
  • Assessed the efficacy of PLK1 inhibition and its relation to volasertib resistance.

Main Results:

  • Cisplatin-resistant cells exhibit increased spindle checkpoint activity and rely on PLK1 for mitotic exit despite APC/C dysfunction.
  • PLK1 inhibition reduced survival of resistant cells and enhanced spindle checkpoint response.
  • Resistance to the PLK1 inhibitor volasertib is linked to low PLK1 expression.

Conclusions:

  • Discovered APC/C dysfunction in cisplatin-resistant cells, suggesting novel mitotic exit-based therapies.
  • PLK1 downregulation is a mechanism for resistance to PLK1-targeted therapies in cancer.

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