Abstract | PURPOSE: Aberrant activation of protein kinase Cbeta (PKCbeta) by pancreatic cancer cells facilitates angiogenesis and tumor cell survival. Targeting PKCbeta with enzastaurin, a well-tolerated drug in clinical trials, would be expected to radiosensitize pancreatic tumors through direct antitumor and antivascular effects. EXPERIMENTAL DESIGN: RESULTS: CONCLUSIONS:
Enzastaurin inhibits PKCbeta in pancreatic cancer cells in culture, enhancing radiation cytotoxicity. Additional antivascular effects of enzastaurin were observed in vivo, resulting in greater radiosensitization. These results provide the rationale for a clinical trial in locally advanced pancreatic cancer combining enzastaurin with radiation.
|
Authors | Aaron C Spalding, Richard Watson, Mary E Davis, Alex C Kim, Theodore S Lawrence, Edgar Ben-Josef |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 13
Issue 22 Pt 1
Pg. 6827-33
(Nov 15 2007)
ISSN: 1078-0432 [Print] United States |
PMID | 18006785
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Indoles
- Protein Kinase Inhibitors
- GSK3B protein, human
- Glycogen Synthase Kinase 3 beta
- Gsk3b protein, mouse
- Protein Kinase C
- Protein Kinase C beta
- Glycogen Synthase Kinase 3
- enzastaurin
|
Topics |
- Animals
- Glycogen Synthase Kinase 3
(antagonists & inhibitors, metabolism)
- Glycogen Synthase Kinase 3 beta
- Humans
- Indoles
(pharmacology)
- Mice
- Mice, Nude
- Pancreatic Neoplasms
(enzymology, pathology)
- Phosphorylation
- Protein Kinase C
(antagonists & inhibitors)
- Protein Kinase C beta
- Protein Kinase Inhibitors
(pharmacology)
- Radiation Tolerance
(drug effects)
- Tumor Cells, Cultured
- Xenograft Model Antitumor Assays
|