Pharmacogenetics and Pharmacogenomics of Colorectal Cancer: Moving Towards Personalized Medicine

摘要: Colorectal cancer (CRC) remains one of the most deadly diseases in western world, and starts to become a concern developed countries (Labianca et al., 2010). However, significant steps have been made recently CRC therapy. Until 80’s, 5-fluorouracil (5FU) was only available drug treat patients, with limited efficacy. Today, 4 cytotoxic agents (5-FU associated folinic acid, capecitabine, oxaliplatin, irinotecan) three monoclonal antibodies (cetuximab, panitumumab, bevacizumab) are available, mostly as part combinations (Koutras 2011). In particular, rise targeted therapies digestive oncology has fueled new hope by significantly stretching therapeutic options so far. Despite these improvements, treatment metastatic (mCRC) challenging task, it is acknowledged now that although improving response rates, introduction latest marginally impacts on either progression free survival (PFS) or overall (OS) mCRC patients. Because cost therapies, identifying biomarkers likely sort patients their ability benefit not, from drugs paradigmatic current trend move towards more personalized medicine oncology. genetic variability main factor regulating efficacy toxicity anticancer agents, addressing issues pharmacogenomics pharmacogenetics (PGx) patient becomes critical, far beyond use costly therapies. Although often used interchangeably, term “pharmacogenetics” refers historically inherited changes genes coding for metabolizing enzymes membrane transporters, thus impacting pharmacokinetic (PK) profile exposure levels eventually, whereas “pharmacogenomics” broader definition encompassing at tumor level potentially affecting (Amstutz Whether they somatic found germline, all mutations can deleterious clinical outcome cancer. At level, expression pharmacological