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Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness

Patricia S Lorenzo1, Phillip A Dennis

  • 1Natural Products Program, Cancer Research Center of Hawaii, Honolulu, HI 96813, USA.

Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
|January 28, 2004
PubMed

Insights

Targeting protein kinase C (PKC) to overcome chemotherapy resistance in cancer has shown limited success. Further research is needed to understand why PKC modulators combined with chemotherapy failed in recent trials.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Protein kinase C (PKC) isoforms play crucial roles in cellular processes and transformation, making them potential targets for cancer therapy.
  • In vitro studies suggested that modulating PKC activity could impact tumor cell survival and overcome chemotherapy resistance.

Purpose of the Study:

  • To review the development of PKC modulators for cancer treatment.
  • To discuss the reasons behind the limited success of PKC modulators in recent clinical trials.
  • To propose guidelines for future clinical evaluation of PKC modulators.

Main Methods:

  • Review of preclinical and clinical studies on PKC modulators.
  • Analysis of clinical trial data combining PKC modulators with standard chemotherapy.
  • Discussion of potential mechanisms for treatment failure.

Main Results:

  • Early clinical trials showed varied responses to PKC modulators.
  • Recent trials indicated that combining PKC modulators with chemotherapy did not improve outcomes compared to chemotherapy alone.
  • The development of resistance to chemotherapy remains a significant challenge in cancer treatment.

Conclusions:

  • Despite promising in vitro data, clinical application of PKC modulators has faced challenges.
  • Further investigation is required to understand the complex role of PKC in chemoresistance.
  • Revised strategies and guidelines are necessary for the effective clinical evaluation of PKC modulators in cancer therapy.

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