Pharmaceutical Sciences Faculty Publications

Title

Serum Proteomic Profiles Suggest Celecoxib-Modulated Targets and Response Predictors

Document Type

Article

Publication Date

4-15-2004

Journal Title

Cancer Research

ISSN

0008-5472

Volume

64

Issue

8

First Page

2904

Last Page

2909

DOI

10.1158/0008-5472.can-03-3754

PubMed ID

15087410

Abstract

Cyclooxygenase-2 is a valid target for cancer prevention and treatment. This has been shown in preclinical and clinical cancer prevention studies by using a cyclooxygenase-2 inhibitor, celecoxib. When used in a randomized cancer prevention clinical trial on patients with the inherited autosomal dominant condition, familial adenomatous polyposis, celecoxib proved efficacious. However, a remarkable heterogeneity in patients' responses to the chemopreventive effects of celecoxib was observed. Proteomic profiling of sera from these patients identified several markers, the expression of which was specifically modulated after treatment with celecoxib. A decision tree algorithm identified classifiers for response to celecoxib with relatively high sensitivity but moderate to low specificity. In particular, a spectral feature at m/z 16,961.4 was identified as a strong discriminator between response and nonresponse to celecoxib at the highest dose.

Keywords

Adenomatous polyposis coli, anticarcinogenic agents, blood proteins, celecoxib, mass spectrometry, proteome, pyrazoles, sulfonamides

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