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

Patricia S. Lorenzo, Phillip A. Dennis

Research output: Contribution to journalArticle

Abstract

The identification of molecules that promote chemotherapeutic resistance would allow rationally designed approaches to abrogate this resistance, thereby possibly improving clinical outcomes for patients with cancer. In this regard, the PKC family is attractive for targeting, because it is comprised of a family of isoforms that play key roles in multiple cellular processes and can contribute to cellular transformation. Encouraging in vitro data originally showed that approaches to modulate PKC activity through small-molecule inhibitors or genetic manipulation could affect tumor cell survival. Recently, some of these approaches have begun clinical testing. Early-stage clinical trials revealed scattered clinical responses to these agents, but the most recent clinical trials have shown that combining modulators of PKC with standard chemotherapy does not improve outcome over chemotherapy alone. In this review, we will trace the development of these approaches, and discuss possible explanations for the recent negative results. Importantly, we will suggest guidelines for the clinical evaluation of PKC modulators.

Original languageEnglish (US)
Pages (from-to)329-339
Number of pages11
JournalDrug Resistance Updates
Volume6
Issue number6
DOIs
StatePublished - Dec 2003

Keywords

  • Apoptosis
  • Chemotherapy
  • Kinase
  • PKC

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Cancer Research
  • Infectious Diseases
  • Pharmacology (medical)

Fingerprint Dive into the research topics of 'Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: Stepping into darkness'. Together they form a unique fingerprint.

  • Cite this