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Review
. 2025 Nov 20;9(1):369.
doi: 10.1038/s41698-025-01144-9.

MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer

Ming-Sound Tsao  1   2 , Lynette Sholl  3 , Michelle Shiller  4   5 , Peter Illei  6 , Ignacio I Wistuba  7 , Mary Beth Beasley  8 , Kurt A Schalper  9 , Archana Simmons  10 , Peter Ansell  10 , Sue Beruti  10 , Mari Mino-Kenudson  11
Affiliations
Review

MET (c-Met) protein overexpression is an emerging protein biomarker in non-small cell lung cancer

Ming-Sound Tsao et al. NPJ Precis Oncol. .

Abstract

MET protein (also known as c-Met protein) overexpression (OE) is an emerging clinically relevant biomarker that is targetable with antibody-drug conjugates. c-Met protein's prevalence varies, depending on the different OE thresholds, antibodies, and detection methodologies used. Unlike MET genomic aberrations, MET protein OE is a protein biomarker requiring immunohistochemistry (IHC)-based testing. Herein, we summarize the current evidence on MET protein OE, including prognostic value, heterogeneity, and stability. We also provide key considerations for enabling optimal real-world testing of this IHC-based biomarker.

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Conflict of interest statement

Competing interests: Ming-Sound Tsao: received compensation as a consultant for AbbVie, AstraZeneca, Daiichi Sankyo, and Sanofi, research grants (to institution) from Sanofi and AstraZeneca. Lynette Sholl: consultant for Genentech, AstraZeneca, Lilly; research funding from Genentech, Bristol Myers Squibb. Michelle Shiller: nothing to disclose. Peter Illei: received compensation as a consultant for AbbVie, AstraZeneca, Sanofi, and Boehringer Ingelheim and a research grant (to institution) from Bristol Myers Squibb. Ignacio I. Wistuba: nothing to disclose. Mary Beth Beasley: received compensation as a consultant and advisory board participant for AbbVie, Sanofi, Daiichi Sankyo, and AstraZeneca. Kurt A. Schalper: consultant or advisor: AbbVie Inc.; Agenus Inc.; AstraZeneca; Bristol Myers Squibb; CDR-Life Inc.; Clinica Alemana de Santiago; EMD Serono Inc.; F. Hoffmann-La Roche; Genmab A/S; Indaptus Therapeutics; Janssen Pharmaceuticals, Inc.; Merck Sharpe & Dohme; Moderna, Inc.; Molecular Templates, Inc.; OnCusp Therapeutics; Parthenon/Incendia Therapeutics; Picture Health, Repertoire Therapeutics; Sanofi; Sensei Biotherapeutics; Shattuck Labs, Inc.; and Takeda Pharmaceutical Company Limited. Funding: Akoya Biosciences; AstraZeneca; Boehringer Ingelheim; Bristol Myers Squibb; F. Hoffmann-La Roche; Lilly; Merck Sharpe & Dohme; Ribon Therapeutics; Surface Oncology; Takeda Pharmaceutical Company Limited; and Tesaro Inc./GSK. Archana Simmons, Peter Ansell, Sue Beruti: employees of AbbVie and may own stock. Mari Mino-Kenudson: has served as a compensated consultant for AstraZeneca, Boehringer Ingelheim, Pfizer, Repare, Sanofi, Daiichi Sankyo, Roche, and AbbVie, and received an honorarium for speaking and travel support from Sanofi and royalties from Elsevier.

Figures

Fig. 1
Fig. 1. Prevalence of MET alterations in non-squamous NSCLC.
ex exon, NSCLC non-small cell lung cancer, OE overexpression.
Fig. 2
Fig. 2. A representative image of MET protein staining.
A 0+, B 1+, C 2+, and D 3+ MET protein staining intensity using the anti-MET protein SP44 clone (Roche Diagnostics).
See this image and copyright information in PMC

References

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