Pharmacogenetic Concerns in Metastatic Colorectal Cancer Therapy
Cet article passe en revue les enjeux associés à l'identification de biomarqueurs prédictifs d'une réponse thérapeutique dans le cancer colorectal métastatique
In recent years statements such “predictive biomarkers are urgently needed” have been the unavoidable conclusion of almost all scientific papers, reviews, and experts’ talks at major symposia. Despite this, and thousands of publications, few biomarkers have reached the clinic. This should not be surprising now we are becoming increasingly aware of the complexity of the behavior of the tumor, its interactions with the host, its changes in response to pharmacological pressure, and how poorly targeted are our targeted drugs. Metastatic colorectal cancer (mCRC) and translational research on this disease, are emblematic examples of the difficulty of discovery and validation of molecular markers for clinical use. The single-nucleotide polymorphism (SNP) approach fascinated many researchers and each drug—from the old chemotherapeutic agents to the new antibodies—currently approved for treatment of mCRC has had its extensive pharmacogenetic translational program. This review chronicles the main steps of the pharmacogenetic story for each agent used in mCRC from the most promising initial data to the failure of their validation, trying to focus on the major pitfalls and to give new suggestions for future research.
Current Colorectal Cancer Reports , résumé, 2011