作者
James J Harding, Maeve A Lowery, Alan H Shih, Juan M Schvartzman, Shengqi Hou, Christopher Famulare, Minal Patel, Mikhail Roshal, Richard K Do, Ahmet Zehir, Daoqi You, S Duygu Selcuklu, Agnes Viale, Martin S Tallman, David M Hyman, Ed Reznik, Lydia WS Finley, Elli Papaemmanuil, Alessandra Tosolini, Mark G Frattini, Kyle J MacBeth, Guowen Liu, Bin Fan, Sung Choe, Bin Wu, Yelena Y Janjigian, Ingo K Mellinghoff, Luis A Diaz, Ross L Levine, Ghassan K Abou-Alfa, Eytan M Stein, Andrew M Intlekofer
发表日期
2018/12/1
期刊
Cancer discovery
卷号
8
期号
12
页码范围
1540-1547
出版商
American Association for Cancer Research
简介
Somatic mutations in cytosolic or mitochondrial isoforms of isocitrate dehydrogenase (IDH1 or IDH2, respectively) contribute to oncogenesis via production of the metabolite 2-hydroxyglutarate (2HG). Isoform-selective IDH inhibitors suppress 2HG production and induce clinical responses in patients with IDH1- and IDH2-mutant malignancies. Despite the promising activity of IDH inhibitors, the mechanisms that mediate resistance to IDH inhibition are poorly understood. Here, we describe four clinical cases that identify mutant IDH isoform switching, either from mutant IDH1 to mutant IDH2 or vice versa, as a mechanism of acquired clinical resistance to IDH inhibition in solid and liquid tumors.
Significance
IDH-mutant cancers can develop resistance to isoform-selective IDH inhibition by “isoform switching” from mutant IDH1 to mutant IDH2 or vice versa, thereby restoring 2HG …
学术搜索中的文章
JJ Harding, MA Lowery, AH Shih, JM Schvartzman… - Cancer discovery, 2018