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Apoptosis-Based Evaluation of Chemosensitivity in Ovarian Cancer Patients

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The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

Induction of apoptosis in target cells is a key mechanism by which chemotherapy induces cell killing. We have established an in vitro system for determining the chemosensitivity of epithelial ovarian cancer cells to carboplatin and paclitaxel (Taxol). Practical assays to predict the likelihood of individual tumor sensitivity are needed to facilitate the choice of adequate treatment. We sought to determine whether epithelial ovarian cancer cells (EOC) collected from the ascites fluid of patients known to be clinically chemosensitive or chemoresistant to carboplatin and paclitaxel would show a similar response to chemotherapeutic drugs after in vitro treatment.

Methods

Thirteen patients with stage III and IV ovarian cancer treated with carboplatin and paclitaxel were studied. Caspase-3 activation was used as a surrogate marker for activation of chemotherapy-induced programmed cell death. We compared the in vitro apoptotic response to the clinical response of the patients from whom the tumor cells were isolated. Clinical sensitivity was defined as no evidence of disease recurrence for 6 months after optimal debulking surgery and completion of chemotherapy.

Results

Of seven chemosensitive patients, five cell samples treated in vitro had increased caspase-3 activity in response to both carboplatin and paclitaxel. Five of six chemoresistant cases did not show caspase-3 activity in response to only one or to neither agent.

Conclusion

Quantifiable markers of apoptosis such as caspase-3 activation have the potential to predict the clinical response to chemotherapy. Application of this assay in clinical laboratories could optimize the potential for efficient treatment and avoid the toxicities of ineffective drugs.

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Authors and Affiliations

  1. Departments of Therapeutic Radiology and Obstetrics and Gynecology, Yale University School of Medicine, Yale Cancer Center, P.O. Box 208063, New Haven, Connecticut, 06520, USA

    Maryann B. Flick PhD, David O’Malley MD, Thomas Rutherford MD, PhD, Sofya Rodov MS, Marijka Kamsteeg MD, Xiao-Ying Hao MD, Peter Schwartz MD, Barry M. Kacinski MD & Gil Mor MD, PhD

Authors
  1. Maryann B. Flick PhD
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  2. David O’Malley MD
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  3. Thomas Rutherford MD, PhD
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  4. Sofya Rodov MS
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  5. Marijka Kamsteeg MD
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  6. Xiao-Ying Hao MD
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  7. Peter Schwartz MD
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  8. Barry M. Kacinski MD
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  9. Gil Mor MD, PhD
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Corresponding author

Correspondence to Gil Mor MD, PhD.

Additional information

This work was supported by a grant from the Ethyl F. Donaghue Foundation to BMK and MBF and by grants from the National Institutes of Health, ROl HD37137-01A2 and R01CA92435-01 to GM.

The authors thank Dr. Reena Jain for assessment of the pathology of the isolated ascites cells, Dr. Bambang Dwipoyono for assistance with caspase-3 assays, and Dr. Eva Sapi for helpful discussions and critical review of the manuscript

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Flick, M.B., O’Malley, D., Rutherford, T. et al. Apoptosis-Based Evaluation of Chemosensitivity in Ovarian Cancer Patients. Reprod. Sci. 11, 252–259 (2004). https://doi.org/10.1016/j.jsgi.2003.11.003

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