Research progress on KRAS mutations in colorectal cancer
作者机构：Department of Medical OncologyOncology Institute of Southern SwitzerlandBellinzona 6500Switzerland Institute of PathologyLaboratory of Molecular PathologyLocarno 6600Switzerland Universitàdella Svizzera ItalianaLugano 6900Switzerland
出 版 物：《Journal of Cancer Metastasis and Treatment》 (癌症转移与治疗（英文版）)
年 卷 期：2021年第7卷第1期
页 面：364-380页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
基 金：Department of Clinical Pharmacology, William Harvey Research Institute, Charterhouse Square, Barts and The London School of Medicine and Dentistry, Queen Mary University of London National Institute on Aging(R01AG007424) Medical Research Council(G108/603, MR/K013351/1, MR/L014815/1, MR/N029488/1) Economic and Social Research Council(ES/J023299/1)
主 题：KRAS targeted therapies EGFR pathway MAPK colorectal cancer
摘 要：The RAS gene family,responsible for signal transduction within the mitogen activated protein kinase(MAPK)and phosphatidylinositol 3 kinase(PI3K)pathways,is frequently involved in carcinogenesis,and alterations in its member genes can be detected,with variable frequency,in a wide variety of solid and hematological *** alterations may behave as prognostic-predictive biomarkers and driver mutations,making them an interesting therapeutic *** their discovery,many strategies have been pursued to act on their signaling ***,in clinical practice,KRAS,the most prominent member of the RAS gene family,represents an especially elusive target in most malignancies;pathway inhibition is carried out upstream,on the EGFR receptor,or downstream,most frequently on the BRAF/MEK/ERK ***,clinically relevant direct RAS inhibition has been successfully achieved with the development of potent and selective covalent inhibitors of KRAS c.34GT(p.G12C).These latest-generation drugs represent both a new and interesting tool in the therapeutic armamentarium and a symbolic end to the myth of KRAS ***,their clinical relevance and appropriate place in treatment strategies remain to be determined.
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