作者
David M Hyman, Sarina A Piha-Paul, Helen Won, Jordi Rodon, Cristina Saura, Geoffrey I Shapiro, Dejan Juric, David I Quinn, Victor Moreno, Bernard Doger, Ingrid A Mayer, Valentina Boni, Emiliano Calvo, Sherene Loi, Albert C Lockhart, Joseph P Erinjeri, Maurizio Scaltriti, Gary A Ulaner, Juber Patel, Jiabin Tang, Hannah Beer, S Duygu Selcuklu, Aphrothiti J Hanrahan, Nancy Bouvier, Myra Melcer, Rajmohan Murali, Alison M Schram, Lillian M Smyth, Komal Jhaveri, Bob T Li, Alexander Drilon, James J Harding, Gopa Iyer, Barry S Taylor, Michael F Berger, Richard E Cutler Jr, Feng Xu, Anna Butturini, Lisa D Eli, Grace Mann, Cynthia Farrell, Alshad S Lalani, Richard P Bryce, Carlos L Arteaga, Funda Meric-Bernstam, José Baselga, David B Solit
发表日期
2018/2/8
期刊
Nature
卷号
554
期号
7691
页码范围
189-194
出版商
Nature Publishing Group UK
简介
Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, ‘basket’ trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven …
学术搜索中的文章
DM Hyman, SA Piha-Paul, H Won, J Rodon, C Saura… - Nature, 2018