, Volume 3, Issue 3, pp 143-149
Date: 08 Jul 2007

Adjuvant therapy for colon cancer based on pharmacogenomics?

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Abstract

The impact of adjuvant chemotherapy for patients with localized colon adenocarcinoma is obvious for stage III and high-risk stage II patients but remains somewhat controversial for low-risk stage II. Until now, the decision of an adjuvant chemotherapy is based on pathologic and clinical data. However, some important questions remain. In stage III, how can we improve the results? In low-risk stage II patients, who will benefit from adjuvant chemotherapy? In the event that an adjuvant therapy is decided, which drugs will be chosen, and is the patient at high risk of toxicity because of metabolic deficiency? Different approaches have been developed: 1) genetics to detect DNA mutations or variants in the primary tumor or the patient himself, 2) RNA expression quantification either based on microarray or with real-time quantitative reverse transcriptase-polymerase chain reaction, and 3) protein expression by immunohistochemistry. Despite promising results from retrospective or prospective studies, the available data remain insufficient to draw guidelines. Genetics with the detection of microsatellite instability status and loss of heterozygoty is investigated for validation in large international prospective ongoing clinical trials. Some genes, such as excision repair cross complementing 1, thymidylate synthase, mismatch repair seem to be very good candidates to predict sensitivity to certain drugs. Clearly, the major potential interest of biologic markers highlights the need of multicentric prospective clinical trials to answer crucial questions about adjuvant therapy.