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

Publication ,  Journal Article
Lorenzo, PS; Dennis, PA
Published in: Drug Resist Updat
December 2003

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.

Duke Scholars

Published In

Drug Resist Updat

DOI

ISSN

1368-7646

Publication Date

December 2003

Volume

6

Issue

6

Start / End Page

329 / 339

Location

Scotland

Related Subject Headings

  • Treatment Outcome
  • Protein Kinase C
  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Drug Resistance, Neoplasm
  • Drug Resistance, Multiple
  • Clinical Trials as Topic
  • Antineoplastic Combined Chemotherapy Protocols
  • Animals
 

Citation

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ICMJE
MLA
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Lorenzo, P. S., & Dennis, P. A. (2003). Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness. Drug Resist Updat, 6(6), 329–339. https://doi.org/10.1016/j.drup.2003.10.003
Lorenzo, Patricia S., and Phillip A. Dennis. “Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness.Drug Resist Updat 6, no. 6 (December 2003): 329–39. https://doi.org/10.1016/j.drup.2003.10.003.
Lorenzo PS, Dennis PA. Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness. Drug Resist Updat. 2003 Dec;6(6):329–39.
Lorenzo, Patricia S., and Phillip A. Dennis. “Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness.Drug Resist Updat, vol. 6, no. 6, Dec. 2003, pp. 329–39. Pubmed, doi:10.1016/j.drup.2003.10.003.
Lorenzo PS, Dennis PA. Modulating protein kinase C (PKC) to increase the efficacy of chemotherapy: stepping into darkness. Drug Resist Updat. 2003 Dec;6(6):329–339.
Journal cover image

Published In

Drug Resist Updat

DOI

ISSN

1368-7646

Publication Date

December 2003

Volume

6

Issue

6

Start / End Page

329 / 339

Location

Scotland

Related Subject Headings

  • Treatment Outcome
  • Protein Kinase C
  • Oncology & Carcinogenesis
  • Neoplasms
  • Humans
  • Drug Resistance, Neoplasm
  • Drug Resistance, Multiple
  • Clinical Trials as Topic
  • Antineoplastic Combined Chemotherapy Protocols
  • Animals