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

Author:

Tejpar Sabine1,Bertagnolli Monica2,Bosman Fred3,Lenz Heinz-Joseph4,Garraway Levi5,Waldman Frederic6,Warren Robert7,Bild Andrea8,Collins-Brennan Denise2,Hahn Hejin9,Harkin D. Paul10,Kennedy Richard10,Ilyas Mohammad11,Morreau Hans12,Proutski Vitali10,Swanton Charles13,Tomlinson Ian14,Delorenzi Mauro15,Fiocca Roberto16,Van Cutsem Eric1,Roth Arnaud17

Affiliation:

1. a Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium

2. b Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA

3. c Department of Pathology, Lausanne University, Lausanne, Switzerland

4. d Keck School of Medicine, University of Southern California, Los Angeles, California, USA

5. e Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA

6. f Department of Urology, University of California, San Francisco, CA, USA

7. g Department of Surgery, University of California, San Francisco, CA, USA

8. h Department of Pharmacology & Toxicology, University of Utah, Salt Lake City, Utah, USA

9. i Department of Pathology, Virginia Mason Medical Center, Seattle, Washington, USA

10. j Almac Diagnostics, Cambridge, Massachusetts, USA

11. k School of Molecular Medical Sciences, University of Nottingham, Nottingham, UK

12. l Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

13. m Cancer Research UK, London Research Institute, Royal Marsden Hospital, London, UK

14. n Molecular and Population Genetics Laboratory, London Research Institute, Cancer Research UK, London, UK

15. o Swiss Institute of Bioinformatics, Lausanne, Switzerland

16. p Department of Surgical and Morphological Science, University of Genova, Genova, Italy

17. q Oncosurgery, University Hospital of Geneva, Geneva, Switzerland

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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