Targeted therapy of cancer: New roles for pathologists in colorectal cancer

摘要: Personalized/individualized/tailored therapy for each patient is an important goal improving the outcome of patients with colorectal adenocarcinoma and includes intention to maximize efficacy minimize toxicity chemotherapeutic agents. Numerous barriers must be overcome reach this because affected by unholy trinity tumor characteristics that include somatic alterations at DNA, RNA, protein level; germline genetic differences such as polymorphisms in enzymes affecting metabolism agents; environmental exposures factors diet physical activity. At present, evaluation epidermal growth factor receptor (EGFR) expression immunohistochemistry generally required treatment one monoclonal antibody therapies directed against target, despite absence evidence predictive value assay, whereas EGFR fluorescent situ hybridization (FISH) may predictive. In addition, Food Drug Administration United States now requires a 'black box' warning on packaging irinotecan polymorphism UGT1A1, gene mutated Gilbert's syndrome, potential reduction drug dosage UGT1A1*28 polymorphism. other markers have been identified but not yet reached levels support their routine usage. For example, KRAS mutation appears preclude improved survival after EGFR, extensive DNA methylation associated lack 5-fluorouracil (5-FU)-based chemotherapy. Additional will come into usage reports research studies continue appear literature. Clinical trials driven molecular targets agents them, understanding conflicting data utility reported literature, are needed advance field.