Evidence map›Paper›PMID 40946111›Full record

ArticleBritish journal of cancer2025

Integrative proteo-genomic profiling uncovers key biomarkers of lapatinib resistance in HER2-positive breast cancer.

J Steggall, V Rajeeve, N Al-Subaie, A Naeem, A Ikram, A Naeem, A Hayat

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Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

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0cells of the map it votes in
2citing papers in PubMed
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1 · What the graph read from it

What it found

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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.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

7 authors.

J SteggallDepartment of Molecular and Biomedical Sciences, City St George's, University of London, London, UK.
V RajeeveMass Spectrometry Facility, Barts Cancer Institute, Queen Mary University of London, John Vane Science Centre, London, UK.ORCID http://orcid.org/0000-0002-6361-4291
N Al-SubaieDepartment of Mathematics and Statistics, Al-Khurmah University College, Taif University, Taif, Saudi Arabia.
A NaeemDepartment of Molecular and Biomedical Sciences, City St George's, University of London, London, UK.
A IkramDepartment of Molecular and Biomedical Sciences, City St George's, University of London, London, UK.
A NaeemDepartment of Basic Sciences, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia.
A HayatDepartment of Molecular and Biomedical Sciences, City St George's, University of London, London, UK. ahayat@sgul.ac.uk.ORCID http://orcid.org/0000-0003-0277-7668

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionDrug resistance is a major obstacle to the long-term effectiveness of cancer therapies. Approximately 70% of breast cancer patients relapse after 5 years of treatment, and the lack of biomarkers associated with drug resistance translates to poor prognosis in the clinic. Previous research has utilised omics approaches to uncover biomarkers driving drug resistance, with a strong emphasis on genetic mutations.

methodsHere, we identified a nine-marker signature associated with resistance to lapatinib in a HER2-positive breast cancer model using a target discovery approach by employing an integrative multi-omics strategy, combining ATAC-seq, RNA-seq and proteomics.

resultsWe found that seven markers in the drug resistance-signature had not been previously found to be implicated in HER2-positive breast cancer, some of which we further validated using an additional lung cancer model. We counterintuitively found that drug-resistant cells have restrictive chromatin accessibility with reduced gene expression associated with limited total proteome changes. However, upon closer look, we identified that the drug resistance-signature had increased chromatin accessibility near the transcriptional start sites of those seven markers and was highly differentially expressed across the three datasets. Our data show that despite the overall transcriptional and proteomic landscape showing limited changes, there are several markers that are highly expressed, which correlate with increased anchorage-independent and invasive phenotype in vitro in lapatinib-resistant cells compared to cancer cells.

conclusionsOur results demonstrate that disease aggressiveness can be related to reduced chromatin and gene expression dynamics. We anticipate that the resistant signature identified here using an integrative target discovery approach can be applied to complex, more representative models and validated before they can be targeted by suitable therapeutic agents.

Indexed as

Biomarkers, TumorBreast NeoplasmsDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesLapatinibAntineoplastic AgentsCell Line, TumorFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHumansProteogenomicsProteomicsAntineoplastic AgentsBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesLapatinib

Identifiers

PMID40946111
PMCPMC12603111

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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.