Serum proteomic profiles suggest celecoxib-modulated targets and response predictors.
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.
Xiao
Zhen
Z
Laboratory of Proteomics and Analytical Technologies and Advanced Biomedical Computing Center, SAIC-Frederick Inc., National Cancer Institute at Frederick, Frederick, Maryland, USA.
Luke
Brian T
BT
Izmirlian
Grant
G
Umar
Asad
A
Lynch
Patrick M
PM
Phillips
Robin K S
RK
Patterson
Sherri
S
Conrads
Thomas P
TP
Veenstra
Timothy D
TD
Greenwald
Peter
P
Hawk
Ernest T
ET
Ali
Iqbal U
IU
D011125:Adenomatous Polyposis Coli / Q000097:blood* / Q000235:genetics / Q000517:prevention & control; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001798:Blood Proteins / Q000378:metabolism*; D000068579:Celecoxib; D017322:Clinical Trials, Phase II as Topic; D020022:Genetic Predisposition to Disease; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D020543:Proteome / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles; D016032:Randomized Controlled Trials as Topic; D013449:Sulfonamides / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D001798:Blood Proteins; D020543:Proteome; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib