Ontology highlight
ABSTRACT:
SUBMITTER: Sudhan DR
PROVIDER: S-EPMC7301608 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
Sudhan Dhivya R DR Guerrero-Zotano Angel A Won Helen H González Ericsson Paula P Servetto Alberto A Huerta-Rosario Mariela M Ye Dan D Lee Kyung-Min KM Formisano Luigi L Guo Yan Y Liu Qi Q Kinch Lisa N LN Red Brewer Monica M Dugger Teresa T Koch James J Wick Michael J MJ Cutler Richard E RE Lalani Alshad S AS Bryce Richard R Auerbach Alan A Hanker Ariella B AB Arteaga Carlos L CL
Cancer cell 20200123 2
We developed neratinib-resistant HER2-mutant cancer cells by gradual dose escalation. RNA sequencing identified TORC1 signaling as an actionable mechanism of drug resistance. Primary and acquired neratinib resistance in HER2-mutant breast cancer patient-derived xenografts (PDXs) was also associated with TORC1 hyperactivity. Genetic suppression of RAPTOR or RHEB ablated P-S6 and restored sensitivity to the tyrosine kinase inhibitor. The combination of the TORC1 inhibitor everolimus and neratinib ...[more]