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Resistance to alkylating agents and cisplatin: insights from ovarian carcinoma model systems

R P Perez1, T C Hamilton, R F Ozols

  • 1Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111.

Pharmacology & Therapeutics
|January 1, 1990
PubMed

Insights

Ovarian cancer chemotherapy resistance, often due to platinum and alkylating agents, can be overcome. Targeting glutathione and DNA repair mechanisms partially reverses this resistance in cell lines, offering new treatment strategies.

Area of Science:

  • Oncology
  • Cancer Biology
  • Pharmacology

Background:

  • Chemotherapy resistance limits ovarian cancer treatment efficacy.
  • Platinum and alkylating agents are common chemotherapeutics for ovarian cancer.
  • Mechanisms of resistance include altered drug transport, increased sulfhydryl molecules, and enhanced DNA repair.

Purpose of the Study:

  • To investigate mechanisms of platinum and alkylating agent resistance in ovarian cancer.
  • To develop chemoresistant ovarian cancer cell lines for study.
  • To evaluate strategies for overcoming chemoresistance.

Main Methods:

  • Development of multiple ovarian cancer cell lines resistant to platinum compounds and alkylating agents.
  • Quantification of glutathione levels and assessment of DNA repair activity.
  • In vitro testing of resistance modulation using buthionine sulfoximine (BSO) and other agents.

Main Results:

  • Resistant cell lines exhibited increased glutathione levels and enhanced DNA repair.
  • These two factors were major determinants of the chemoresistant phenotype.
  • Treatment with BSO and other agents partially reversed in vitro chemoresistance.

Conclusions:

  • Increased glutathione and enhanced DNA repair are key mechanisms of ovarian cancer chemoresistance.
  • Modulating these pathways offers a potential strategy to overcome resistance.
  • Clinical investigations into similar treatment strategies are warranted.

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