ArticleCancer cell2020
Hyperactivation of TORC1 Drives Resistance to the Pan-HER Tyrosine Kinase Inhibitor Neratinib in HER2-Mutant Cancers.
Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Application and prospect of organoid technology in breast cancer.Frontiers in immunology · 2024Pooled it
- Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Trial
- Advancements in Drug Discovery Techniques for Cancer Treatment: Clinical Progress and Future Directions.Current drug discovery technologies · 2026Review
- The role of genetics and epigenetics in breast cancer: A comprehensive review of metastasis, risk factors, and future perspectives.Journal of pharmaceutical analysis · 2025Review
- Review
- Cisplatin-encapsulated TRAIL-engineered exosomes from human chorion-derived MSCs for targeted cervical cancer therapy.Stem cell research & therapy · 2024Article
- Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer.Oncogenesis · 2024Article
- HER2 mutation as an emerging target in advanced breast cancer.Cancer science · 2024Review
- Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models.British journal of cancer · 2024Article
- Design, Synthesis, and Biological Evaluation of Newly Synthesized Cinnamide-Fluorinated Containing Compounds as Bioactive Anticancer Agents.ACS omega · 2024Article
- Neratinib for HER2-positive breast cancer with an overlooked option.Molecular medicine (Cambridge, Mass.) · 2023Review
- Combined blockade of mTOR and p21-activated kinases pathways prevents tumour growth in KRAS-mutated colorectal cancer.British journal of cancer · 2023Article
- Dramatic Response to Pyrotinib and T-DM1 in HER2-Negative Metastatic Breast Cancer With 2 Activating HER2 Mutations.The oncologist · 2023Article
- Establishment and Culture of Patient-Derived Breast Organoids.Journal of visualized experiments : JoVE · 2023Article
- Review
- Molecular targeted therapy for anticancer treatment.Experimental & molecular medicine · 2022Review
- Neratinib causes non-recoverable gut injury and reduces intestinal cytochrome P450 3A enzyme in mice.Toxicology research · 2022Article
- Mechanisms of neratinib resistance inCancer drug resistance (Alhambra, Calif.) · 2022Review
- Molecular vulnerabilities and therapeutic resistance in hormone receptor positive and HER2 dependent breast cancer tumours.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Genome-wide CRISPR-cas9 knockout screening identifies GRB7 as a driver for MEK inhibitor resistance in KRAS mutant colon cancer.Oncogene · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
22 authors at 7 institutions in 1 country.
Funding
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 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 potently arrested the growth of neratinib-resistant xenografts and organoids established from neratinib-resistant PDXs. RNA and whole-exome sequencing revealed RAS-mediated TORC1 activation in a subset of neratinib-resistant models. DNA sequencing of HER2-mutant tumors clinically refractory to neratinib, as well as circulating tumor DNA profiling of patients who progressed on neratinib, showed enrichment of genomic alterations that converge to activate the mTOR pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.