Accession Number:

ADA533483

Title:

Role of Cyclin E as an Early Event in Ovarian Carcinogenesis

Descriptive Note:

Annual summary rept. 1 Apr 2009-30 Mar 2010

Corporate Author:

CEDARS-SINAI MEDICAL CENTER LOS ANGELES CA

Personal Author(s):

Report Date:

2010-04-01

Pagination or Media Count:

30.0

Abstract:

Cyclin E amplification and overexpression characterizes a subset of epithelial ovarian cancers. We hypothesized that this subset of tumors may demonstrate an enhanced response to targeted therapy with the proteasome inhibitor, bortezomib. Cyclin E also exists in multiple low molecular weight LMW isoforms in cancer cells which demonstrate greater neoplastic activity. A natural dietary phytochemical called Indole-3-Carbinol I3C disrupts cyclin E processing through the inhibition of the enzyme that cleaves cyclin E into its LMW isoforms. When combining I3C with bortezomib, we found I3C to synergistically sensitize ovarian cancer cells to bortezomib. This finding has translational potential as bortezomib as a singleagent was found to have minimal activity in a phase II treatment trial of recurrent ovarian cancer. This finding could re-introduce bortezomib to the therapeutic armamentarium against ovarian cancer if the in vitro results replicate in mice and humans.

Subject Categories:

  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE