Evidence map›Paper›PMID 41406940›Full record

ArticleCell reports. Medicine2025

Lung adenocarcinoma surfaceome remodeling with EGFR inhibitors uncovers placental alkaline phosphatase as a target for combination therapy.

Yihui Chen, Rongzhang Dou, Monica J Hong, Hanwen Xu, Jody Vykoukal, Ricardo A León-Letelier, Yining Cai, Soyoung Park, Ehsan Irajizad, Fu Chung Hsiao and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
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

15 authors.

Yihui ChenDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rongzhang DouDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Monica J HongDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hanwen XuDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jody VykoukalDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ricardo A León-LetelierDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yining CaiDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Soyoung ParkDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ehsan IrajizadDepartment of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Fu Chung HsiaoDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jennifer B DennisonDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Edwin J OstrinDepartment of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Johannes F FahrmannDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Hiroyuki KatayamaDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Samir M HanashDepartment of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: shanash@mdanderson.org.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Treatment of lung adenocarcinomas (LUADs) that exhibit activated epidermal growth factor receptor (EGFR) with EGFR tyrosine kinase inhibitors (TKIs) has limited efficacy. Assessment of the impact of EGFR TKI on the LUAD surfaceome remodeling reveals potential therapeutic targets. We identify placental type alkaline phosphatase (ALPP), which has restricted expression in normal tissues, among upregulated surface proteins following EGFR TKI treatment of both TKI sensitive as well as resistant cells. EGF treatment represses ALPP expression, whereas EGFR TKIs upregulate its expression through dephosphorylation and activation of FoxO3a, a transcriptional regulator that binds to the promoter region of ALPP. The combination of EGFR TKI plus ALPP antibody conjugated with monomethyl auristatin F enhances tumor killing in osimertinib-sensitive and -resistant LUAD models compared to either treatment alone. Our findings support a combination therapy involving an EGFR inhibitor together with an ALPP antibody drug conjugate for EGFR-mutated LUADs.

Indexed as

Adenocarcinoma of LungAlkaline PhosphataseLung NeoplasmsProtein Kinase InhibitorsAnimalsCell Line, TumorDrug Resistance, NeoplasmErbB ReceptorsFemaleForkhead Box Protein O3Gene Expression Regulation, NeoplasticGPI-Linked ProteinsHumansIsoenzymesMiceMice, NudeAlkaline Phosphatasealkaline phosphatase, placentalEGFR protein, humanErbB ReceptorsForkhead Box Protein O3FOXO3 protein, humanGPI-Linked ProteinsIsoenzymesProtein Kinase Inhibitorsantibody drug conjugateEGFRlung adenocarcinomasplacental-type alkaline phosphatase

Identifiers

PMID41406940
PMCPMC12765945

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Registered trials

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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.