Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.
The number of agents that are potentially effective in the adjuvant treatment of locally advanced resectable colon cancer is increasing. Consequently, it is important to ascertain which subgroups of patients will benefit from a specific treatment. Despite more than two decades of research into the molecular genetics of colon cancer, there is a lack of prognostic and predictive molecular biomarkers with proven utility in this setting. A secondary objective of the Pan European Trials in Adjuvant Colon Cancer-3 trial, which compared irinotecan in combination with 5-fluorouracil and leucovorin in the postoperative treatment of stage III and stage II colon cancer patients, was to undertake a translational research study to assess a panel of putative prognostic and predictive markers in a large colon cancer patient cohort. The Cancer and Leukemia Group B 89803 trial, in a similar design, also investigated the use of prognostic and predictive biomarkers in this setting. In this article, the authors, who are coinvestigators from these trials and performed similar investigations of biomarker discovery in the adjuvant treatment of colon cancer, review the current status of biomarker research in this field, drawing on their experiences and considering future strategies for biomarker discovery in the postgenomic era.
Tejpar
Sabine
S
Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium. sabine.tejpar@uz.kuleuven.ac.be
Bertagnolli
Monica
M
Bosman
Fred
F
Lenz
Heinz-Joseph
HJ
Garraway
Levi
L
Waldman
Frederic
F
Warren
Robert
R
Bild
Andrea
A
Collins-Brennan
Denise
D
Hahn
Hejin
H
Harkin
D Paul
DP
Kennedy
Richard
R
Ilyas
Mohammad
M
Morreau
Hans
H
Proutski
Vitali
V
Swanton
Charles
C
Tomlinson
Ian
I
Delorenzi
Mauro
M
Fiocca
Roberto
R
Van Cutsem
Eric
E
Roth
Arnaud
A
D014408:Biomarkers, Tumor; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D016158:Genes, p53 / Q000235:genetics; D042822:Genomic Instability; D023281:Genomics; D006801:Humans; D053842:Microsatellite Instability; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics
D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins