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Gastrointestinal Cancer

Prognostic and Predictive Biomarkers in Resected Colon Cancer: Current Status and Future Perspectives for Integrating Genomics into Biomarker Discovery

^aDigestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium; ^bDepartment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA; ^cDepartment of Pathology, Lausanne University, Lausanne, Switzerland; ^dKeck School of Medicine, University of Southern California, Los Angeles, California, USA; ^eMedical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA; ^fDepartment of Urology and ^gDepartment of Surgery, University of California, San Francisco, CA, USA; ^hDepartment of Pharmacology & Toxicology, University of Utah, Salt Lake City, Utah, USA; ⁱDepartment of Pathology, Virginia Mason Medical Center, Seattle, Washington, USA; ^jAlmac Diagnostics, Cambridge, Massachusetts, USA; ^kSchool of Molecular Medical Sciences, University of Nottingham, Nottingham, UK; ^lDepartment of Pathology, Leiden University Medical Center, Leiden, The Netherlands; ^mCancer Research UK, London Research Institute, Royal Marsden Hospital, London, UK; ⁿMolecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK; ^oSwiss Institute of Bioinformatics, Lausanne, Switzerland; ^pDepartment of Surgical and Morphological Science, University of Genova, Genova, Italy; ^qOncosurgery, University Hospital of Geneva, Geneva, Switzerland

Correspondence: Sabine Tejpar, M.D., Ph.D., Digestive Oncology Unit, University Hospital Gasthuisberg, Herestraat 49, B - 3000 Leuven, Belgium. Telephone: 32-16-344218; Fax: 32-16-344419; E-mail: sabine.tejpar{at}uz.kuleuven.ac.be

Received September 28, 2009; accepted for publication February 22, 2010; first published online in THE ONCOLOGIST Express on March 29, 2010.

Disclosures: Sabine Tejpar: None; Monica Bertagnolli: Honoraria: Pfizer; Fred Bosman: Research funding/contracted research: Pfizer; Heinz-Joseph Lenz: Intellectual property rights/inventor/patent holder: Abraxis; Research funding/contracted research: Genentech, ImClone, Roche, BMS, Merck, Pfizer; Ownership interest: Responsegenetics; Levi Garraway: Consultant/advisory role: Novartis; Research funding/contracted research: Novartis; Frederic Waldman: None; Robert Warren: Research funding/contracted research: NCCN; Andrea Bild: None; Denise Collins-Brennan: None; Hejin Hahn: None; D. Paul Harkin: Employment/leadership position: Almac Diagnostics; Ownership interest: Almac Diagnostics; Richard Kennedy: Employment/leadership position: Almac Diagnostics; Mohammad Ilyas: None; Hans Morreau: None; Vitali Proutski: None; Charles Swanton: None; Ian Tomlinson: None; Mauro Delorenzi: None; Roberto Fiocca: Research funding/contracted research: Pfizer; Eric Van Cutsem: Research funding/contracted research: Pfizer; Arnaud Roth: Honoraria: Pfizer.

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

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.

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