Evidence map›Paper›PMID 42361448›Full record

ArticleESMO open2026

Association of TP53 gain-of-function mutations with early osimertinib resistance in epidermal growth factor receptor-mutant lung adenocarcinoma.

R Ibusuki, E Iwama, A Shimauchi, H Kawano, Y Tsuneoka, M Hashisako, T Harada, Y Tsuchiya-Kawano, K Nakatomi, K Furuyama and 11 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ESMO open, 2026. 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

21 authors.

R IbusukiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
E IwamaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: iwama.eiji.800@m.kyushu-u.ac.jp.
A ShimauchiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
H KawanoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Y TsuneokaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
M HashisakoDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
T HaradaDepartment of Respiratory Medicine, Japan Community Health Care Organization-Kyushu Hospital, Kitakyushu, Japan.
Y Tsuchiya-KawanoDepartment of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
K NakatomiDepartment of Respiratory Medicine, National Hospital Organization Fukuoka Higashi Medical Center, Koga, Japan.
K FuruyamaDepartment of Respiratory Medicine, Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
N NakagakiDepartment of Respiratory Medicine, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
Y KogaDepartment of Respiratory Medicine, Kyushu Central Hospital, Fukuoka, Japan.
S KimuraDepartment of Respiratory Medicine, St. Mary's Hospital, Kurume, Japan.
S MashimotoDepartment of Respiratory Medicine, Steel Memorial Yawata Hospital, Kitakyushu, Japan.
D ShibaharaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
K OtsuboDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Y YoneshimaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Y ShiraishiDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
K TanakaDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Y OdaDepartment of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
I OkamotoDepartment of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe aim of this study was to investigate the clinical and biological impact of TP53 gain-of-function (GOF) mutations in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Although concurrent TP53 mutations are associated with poor outcomes in EGFR-mutant NSCLC, the specific impact of TP53 GOF mutations on resistance to EGFR tyrosine kinase inhibitors has remained unknown. MATERIALS AND

methodsGenomic profiling was performed for pretreatment tumor samples from 140 individuals with advanced or recurrent EGFR-mutant NSCLC who received first-line osimertinib monotherapy. TP53 mutations were functionally classified into GOF and non-GOF mutations. Progression-free survival (PFS) was evaluated according to TP53 status. Underlying biological characteristics of tumors positive for TP53 mutations were explored by transcriptome analysis in 53 patients.

resultsTP53 mutations were detected in 64 (45.7%) of 140 patients, with GOF and non-GOF mutations being identified in 19 (13.6%) and 45 (32.1%) patients, respectively. PFS was significantly shorter in individuals with TP53 GOF mutations than in those wild type for TP53 (median of 12.0 versus 31.4 months, P = 0.0016) or those with TP53 non-GOF mutations (median of 12.0 versus 21.9 months, P = 0.038). The GOF mutations were not associated with baseline clinical features or a reduced objective response rate, suggestive of a role in early development of osimertinib resistance. Transcriptomic analysis revealed upregulation of the ephrin signaling pathway in TP53 GOF-mutant NSCLC.

conclusionsTP53 GOF mutations define a biologically and clinically distinct subtype of EGFR-mutant NSCLC characterized by early resistance to osimertinib.

Indexed as

AcrylamidesAdenocarcinoma of LungAniline CompoundsCarcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmGain of Function MutationLung NeoplasmsTumor Suppressor Protein p53AdultAgedErbB ReceptorsFemaleHumansIndolesMaleMiddle AgedAcrylamidesAniline CompoundsEGFR protein, humanErbB ReceptorsIndolesosimertinibProtein Kinase InhibitorsPyrimidinesTP53 protein, humanTumor Suppressor Protein p53epidermal growth factor receptor (EGFR)gain-of-function mutationosimertinibTP53 mutationtyrosine kinase inhibitor

Identifiers

PMID42361448
PMCPMC13321028

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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.