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Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers

Cancer Cell

Jan 25, 2020

Dhivya R SudhanCarlos L Arteaga

Abstract

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 als...read more

Mentioned in this Paper

Mechanistic target of rapamycin complex 1
RNA
Malignant Neoplasm of Breast
Inhibitors
Tumor Cells, Malignant
Gene Mutant
Drug Resistance
Protein-tyrosine kinase inhibitor
Suppression, Genetic
Ribosomal Protein S6
58
11
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Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers

Cancer Cell

Jan 25, 2020

Dhivya R SudhanCarlos L Arteaga

PMID: 31978326

DOI: 10.1016/j.ccell.2019.12.013

Abstract

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 als...read more

Mentioned in this Paper

Mechanistic target of rapamycin complex 1
RNA
Malignant Neoplasm of Breast
Inhibitors
Tumor Cells, Malignant
Gene Mutant
Drug Resistance
Protein-tyrosine kinase inhibitor
Suppression, Genetic
Ribosomal Protein S6
58
11

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