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Review Article

Chemoprevention, chemotherapy, and chemoresistance in colorectal cancer

, , , , , , & show all
Pages 148-172 | Received 06 May 2011, Accepted 01 Nov 2011, Published online: 12 Apr 2012
 

Abstract

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related death in industrialized countries. Chemoprevention is a promising approach, but studies demonstrating their usefulness in large populations are still needed. Among several compounds with chemopreventive ability, cyclooxygenase inhibitors have received particular attention. However, these agents are not without side effects, which must be weighed against their beneficial actions. Early diagnosis is critical in the management of CRC patients, because, in early stages, surgery is curative in >90% of cases. If diagnosis occurs at stages II and III, which is often the case, neoadjuvant chemotherapy and radiotherapy before surgery are, in a few cases, recommended. Because of the high risk of recurrence in advanced cancers, chemotherapy is maintained after tumor resection. Chemotherapy is also indicated when the patient has metastases and in advanced cancer located in the rectum. In the last decade, the use of anticancer drugs in monotherapy or in combined regimens has markedly increased the survival of patients with CRC at stages III and IV. Although the rate of success is higher than in other gastrointestinal tumors, adverse effects and development of chemoresistance are important limitations to pharmacological therapy. Genetic profiling regarding mechanisms of chemoresistance are needed to carry out individualized prediction of the lack of effectiveness of pharmacological regimens. This would minimize side effects and prevent the selection of aggressive, cross-resistant clones, as well as avoiding undesirable delays in the use of the most efficient therapeutic approaches to treat these patients.

Acknowledgment

The authors thank N. Skinner for revision of the English spelling, grammar, and style of the manuscript for this article.

Declaration of interest

This study was supported, in part, by the following: the Instituto de Salud Carlos III, FIS (grants CP05/0135, PI070517, and PI080151); the Junta de Castilla y León (grants GR75/08, SA033A08, SA03508, and SA036A08), Spain; the Ministerio de Ciencia y Tecnología, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (grants BFU2006–12577 and SAF2009-08493), Spain; Ministerio de Ciencia e Innovación, Spain (grants SAF2010–15517, SAF2008-01432, and AGL2008-04332/ALI); the Fundación Investigación Médica, Mutua Madrileña (Convocatoria 2009), Spain; and the Fundación Ramón Areces. The group is a member of the Network for Cooperative Research on Membrane Transport Proteins (REIT), cofunded by the Ministerio de Educación y Ciencia, Spain, and the European Regional Development Fund (ERDF) (grant BFU2007–30688-E/BFI) and belongs to the CIBERehd (Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas) Instituto de Salud Carlos III, Spain.

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