EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.

doi:10.1038/s41467-026-68424-1

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Community

Back to search

Article

EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.

Nature communications - 14 Jan 2026

Bassil Christopher F, Dillon Kerry, Anderson Gray R, Mayro Benjamin, Askin Kayleigh N, Winter Peter S, Harry Stefan, Gruber Samuel, Hall Tierney M, Hoj Jacob P, Cerda-Smith Christian, Hutchinson Haley M, Killarney Shane T, Heffernan Ava, Teddy Caroline, Singleton Katherine R, Qin Li, Jubien-Girard Kévin, Favreau Cécile, Robert Guillaume, Tivon Barr, Livnah Ella, London Nir, Benhida Rachid, Auberger Patrick, Pendergast Ann Marie, Bar-Peled Liron, Lonard David M, Martin Anthony R, Puissant Alexandre, Wood Kris C

Abstract excerpt

Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a PAINS-like small molecule, MCB-613. Systematic proteomic, functional genomic, and...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Activating Transcription Factor 4

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Carcinoma, Non-Small-Cell Lung

Share to Cysteine

Share to Drug Resistance, Neoplasm

Share to Kelch-Like ECH-Associated Protein 1

Share to Protein Kinase Inhibitors

Share to Protein Multimerization

Share to Reactive Oxygen Species

Source

Open in PubMed Open full text

Identifiers

PMID: 41535280
DOI: 10.1038/s41467-026-68424-1
PMCID: PMC12913772

Genes

KEAP1
EGFR
ATF4

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 3 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.PMID 41535280Read ↗

MCB-613 exploits a collateral sensitivity in drug resistant <i>EGFR</i> -mutant non-small cell lung cancer through covalent inhibition of KEAP1Semantic proximity Read ↗

Targeting mutant EGFR in non-small cell lung cancer in the context of cell adaptation and resistanceSemantic proximity Read ↗

Targeting ubiquitin signaling vulnerabilities in KEAP1-inactivated lung cancer.Semantic proximity Read ↗

KEAP1-Mutant NSCLC: The Catastrophic Failure of a Cell-Protecting Hub.Semantic proximity Read ↗

Perturbation of the mutated EGFR interactome identifies vulnerabilities and resistance mechanisms.Semantic proximity Read ↗

Cancer-derived mutations in KEAP1 impair NRF2 degradation but not ubiquitination.Semantic proximity Read ↗

In vivo functional screens reveal KEAP1 loss as a driver of chemoresistance in small cell lung cancerSemantic proximity Read ↗

Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells.Semantic proximity Read ↗

KEAP1 mutation in lung adenocarcinoma promotes immune evasion and immunotherapy resistance.Semantic proximity Read ↗

Concurrent Mutations in STK11 and KEAP1 Promote Ferroptosis Protection and SCD1 Dependence in Lung Cancer.Semantic proximity Read ↗

Chemoproteomics-Enabled Discovery of a Covalent Molecular Glue Degrader Targeting NF-κBSemantic proximity Read ↗

EMSY inhibits homologous recombination repair and the interferon response, promoting lung cancer immune evasion.Semantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.