Journal article
HER kinase inhibition in patients with HER2-and HER3-mutant cancers
DM Hyman, SA Piha-Paul, H Won, J Rodon, C Saura, GI Shapiro, D Juric, DI Quinn, V Moreno, B Doger, IA Mayer, V Boni, E Calvo, S Loi, AC Lockhart, JP Erinjeri, M Scaltriti, GA Ulaner, J Patel, J Tang Show all
Nature | NATURE PORTFOLIO | Published : 2018
DOI: 10.1038/nature25475
Abstract
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, â €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 b..
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Grants
Awarded by National Institutes of Health
Funding Acknowledgements
We thank patients and their families for participating in this study. Editorial support, not including writing, was provided by L. Miller. This work was funded by Puma Biotechnology, and supported by grants from the National Institutes of Health (grants P30 CA008748, P30 CA016672, P30 CA014089, R01 CA204749, R01 CA80195, T32 CA009207, 1U01 CA180964 and UL1 TR000371), the National Institutes of Health/National Cancer Institute (Breast SPORE grant P50 CA098131), Cycle for Survival, Marie-Josee and Henry R. Kravis Center for Molecular Oncology, The Cancer Prevention and Research Institute of Texas (RP1100584), the Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, Nellie B. Connally Breast Cancer Research Endowment, and the Breast Cancer Research Foundation.