Evidence map›Paper›PMID 42449663›Full record

ReviewCancers2026

HER2 Alterations in Squamous Cell Lung Cancer: Biology, Therapeutic Landscape, and Emerging Precision Approaches.

Dina Elantably, Isabella Meerzaman, Alicia Y Hou, Ahmed Abdelhakeem, Yanyan Lou

Abstract readReview
In one paragraph

Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Dina ElantablyDivision of Haematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.ORCID 0000-0002-4706-3864
Isabella MeerzamanDeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN 37752, USA.
Alicia Y HouDivision of Haematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.ORCID 0000-0002-2572-7711
Ahmed AbdelhakeemDivision of Haematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.
Yanyan LouDivision of Haematology and Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, FL 32224, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Squamous cell lung cancer (SqCLC) accounts for 20-30% of non-small cell lung cancer (NSCLC) and remains associated with a poorer prognosis compared with adenocarcinoma. Despite advances in treatment, 5-year overall survival for advanced (stage IV) disease remains below 10-15%. Unlike non-squamous NSCLC, SqCLC is characterized by a high tumor mutational burden and complex genomic landscape dominated by alterations in tumor suppressor genes and lineage survival pathways including TP53, CDKN2A, PIK3CA, FGFR1, SOX2, and the NFE2L2/KEAP1 oxidative stress pathway, as well as dysregulation of the NOTCH signaling pathway, but it harbors relatively few actionable oncogenic drivers, resulting in limited treatments for targeted therapy. HER2 alterations can occur by multiple mechanisms, including activating mutations, gene amplifications, and protein overexpression. They comprise a very small percentage of NSCLC, with HER2 mutations reported in approximately 1-3% and HER2 amplifications observed roughly in 2-4%. While HER2 alterations are well characterized in lung adenocarcinoma, the prevalence, genomic context, and clinical significance of HER2 alterations in SqCLC remain incompletely defined. Advances in next-generation sequencing have led to improved ability to detect HER2 alterations and facilitated the development of HER2 targeted therapies. Available treatments for advanced/metastatic SqCLC have been historically limited to platinum-doublet chemotherapy, with immune checkpoint inhibitors such as anti-PD-1/PD-L1 newly emerging in the past decade. Selective HER2 tyrosine kinase inhibitors and HER2 antibody/drug conjugates have shown improved efficacy in HER2-altered NSCLC as shown in DESTINY-LUNG02 and BEAMION LUNG-1 trials; however, most of the enrolled patients had non-squamous histology, with minimal or no SqCLC-specific efficacy data reported. Future progress in HER2-altered SqCLC will require inclusion of SqCLC in HER2 basket trials, incorporation of comprehensive molecular profiling and standardized HER2 testing in squamous histology. This review summarizes the current state of knowledge of HER2 biology in SqCLC and highlights areas for future directions for precision oncology in SqCLC.

Indexed as

antibody/drug conjugatesERBB2HER2HER2 biomarkersimmunohistochemistry (IHC)next-generation sequencing (NGS)NSCLCprecision oncologysquamous cell lung cancertargeted therapy

Identifiers

PMID42449663
PMCPMC13360100

What Socratic holds

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LicenceCC BY
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Registered trials

None linked

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 Socratic graph.