Current Perspective Recent advances in the management of colorectal cancer E. Van Cutsem a, *, M. Dicato b , J. Wils c a Department of Internal Medicine, University Hospital Gosthuisberg, Herestraat 49, BE-3000 Leuven, Belgium b Luxembourg Medical Centre, Luxembourg c Laurentius Hospital, Roermond, The Netherlands Received 6 February 2001; received in revised form 12 July 2001; accepted 12 July 2001 1. Introduction After several decades of modest progress in the man- agement of colorectal cancer, the recent identification of colorectal cancer genes, increased understanding of colorectal carcinogenesis, the introduction of new chemotherapeutic agents and the identification of new biological targets have all led to substantial improve- ments in survival and quality of life (QoL) of patients. This progress has also raised hopes for further improvements in the near future. This paper reviews the current ‘state of the art’ in colorectal cancer manage- ment and the impact of recent innovations. 2. Molecular biology, prevention and screening of colorectal cancer 2.1. Molecular mechanisms and chemoprevention of colorectal cancer The importance of the adenoma–carcinoma sequence in the development of colorectal cancer is well estab- lished and recent research has helped to further eluci- date the mechanisms involved in the pathogenesis of this disease. Results of recent studies suggest that the adenomatous polyposis coli (APC) gene may well be the ultimate ‘gatekeeper’ of colonic epithelial cell prolifera- tion. Mutations in the APC gene, which controls the Wnt signal transduction pathway through regulation of b-catenin expression [1,2], may result in unregulated b- catenin expression with subsequent tumorigenic effects [3]. Improved understanding of the molecular processes has revealed new targets for chemoprevention, and potentially suppression or reversal of the carcinogenic process. Among the most extensively evaluated chemopreven- tive strategies for colorectal cancer are the non-steroidal anti-inflammatory drugs (NSAIDs). NSAIDs have been shown to cause reduction and regression of polyps in familial adenomatous polyposis (FAP) [4], but have no consistent effect on duodenal neoplasia. The long-term gastro-intestinal side-effects of these agents have also raised concerns. Another approach involving disruption of cyclo-oxygenase (COX)-2 activity appears more pro- mising, particularly as most colorectal adenomas and cancers overexpress the COX-2 gene [5]. In animal models of COX-2 overexpression, tumour growth can be blocked through inhibition of COX-2 [6]. More recently, the selective COX-2 inhibitor celecoxib has been shown to significantly decrease polyps in FAP [7], resulting in approval of celecoxib by the United States Food and Drug Administration for the management of rectal polyps in patients with the FAP syndrome. This and other COX-2 inhibitors (rofecoxib) in clinical development may also have potential in the secondary prevention of sporadic adenoma recurrence after ade- noma, polyp or tumour removal. These agents are particularly attractive because of their good safety profile. 2.2. Screening Screening for colorectal cancer has numerous ethical implications, and the psychosocial issues and problems of confidentiality for patients and family members must always be considered when conducting screening tests. Counselling is an important component of the process 0959-8049/01/$ - see front matter # 2001 Elsevier Science Ltd. All rights reserved. PII: S0959-8049(01)00249-0 European Journal of Cancer 37 (2001) 2302–2309 www.ejconline.com * Corresponding author. Tel.: +32-16-344225; fax: +32-16- 344419. E-mail address: eric.vancutsem@uz.kuleuven.ac.be (E. Van Cutsem).