Targeting MET in Advanced and Metastatic Non-Small Cell Lung Cancer - A Literature Review of the Current Landscape

Sep 30, 2026

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MET alterations are recognized as both primary oncogenic drivers and mechanisms of acquired resistance in advanced and metastatic non-small cell lung cancer (NSCLC). The review synthesizes current evidence on diagnostic and classification considerations for MET-altered disease, covering key biology and epidemiology. It summarizes treatment outcomes and ongoing investigations across MET tyrosine kinase inhibitors, anti-MET/HGF antibodies, bispecific antibodies, antibody-drug conjugates, and immunotherapy. Emphasis is placed on biomarker-driven patient selection, resistance management, and future multi-omics and therapeutic development priorities.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages26

Reading Time1 h 6 min

AccessFree to download

Background and Objective

Methods

Key Content and Findings

Biomarker types and epidemiology

Treatment strategies and active investigation

Challenges and emerging resistance

Conclusions

References and Publication Details

Targeting MET in advanced and metastatic non-small cell lung cancer: a literature review of the current landscape Amanda Herrmann^, Christopher Grant^, Lyudmila Bazhenova^ UC San Diego Moores Cancer Center, University of California San Diego, La Jolla, CA, USA Contributions: (I) Conception and design: A Herrmann, L Bazhenova; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: All authors; (V) Data analysis and interpretation: None; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors. Correspondence to: Amanda Herrmann, MD. UC San Diego Moores Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA 92093-0658, USA. Email: [aherrmann@health.ucsd.edu](aherrmann@health.ucsd.edu). Background and Objective: MET alterations have been identified as both primary oncogenic drivers and drivers of acquired resistance in non-small cell lung cancer (NSCLC). There are several mechanisms by which the MET axis can become altered, and an evolving understanding of these pathways provides insight into unique therapeutic targets. Despite considerable research and numerous strategies under investigation, challenges remain, and approved therapies are limited. The purpose of this review is to provide an updated summary of the current evidence, key challenges, and future directions for the diagnosis, classification, and management of advanced and metastatic NSCLC harboring MET alterations. Methods: A broad literature review was conducted using key terms related to MET-alterations and targeted therapy in advanced and metastatic NSCLC. While no definitive inclusion or exclusion criteria were applied, articles were selected based on their relevance and rigor, with an emphasis on primary and secondary literature published within the last 10 years. Key Content and Findings: We review here the pathophysiology and epidemiology of MET alterations that have been identified in NSCLC, including MET exon 14 skipping mutation (METex14), MET amplification (MET AMP), MET overexpression (MET OE), and MET fusion (MET FUS) . We review data supporting established treatment strategies as well as areas of active investigation, with a focus on MET tyrosine kinase inhibitors (TKIs), anti-MET and anti-hepatocyte growth factor (HGF) antibodies, bispecific antibodies (B-Abs), antibody-drug conjugates (ADCs), and immunotherapy (IO). We identify key challenges to progress in this space, including standardization of biomarker-driven patient selection, identification of novel therapeutic mechanisms, and management of emerging treatment resistance. Finally, we discuss future directions and areas of promising development, including multi-omics diagnostic approaches, ADCs, and B-Abs. Conclusions: MET-altered NSCLC is a challenging and heterogeneous molecular subset, and our knowledge is rapidly evolving. Work is ongoing to define the spectrum of actionable mutations, to develop standardized and clinically meaningful biomarker-driven identification of these alterations, and to determine the most effective treatment approaches, with the goal of expanding the treatment landscape and improving outcomes for a subset of patients with limited treatment options. Keywords: Non-small cell lung cancer (NSCLC); MET exon 14 skipping (METex14); MET amplification (MET AMP); MET overexpression (MET OE); MET fusion (MET FUS) Submitted May 15, 2025. Accepted for publication Nov 11, 2025. Published online Dec 29, 2025. doi: 10.21037/tcr-2025-1007 View this article at: [https://dx.doi.org/10.21037/tcr-2025-1007](https://dx.doi.org/10.21037/tcr-2025-1007) ^ ORCID: Amanda Herrmann, 0009-0009-2590-8262; Christopher Grant, 0009-0001-6432-5635; Lyudmila Bazhenova, 0000-0001-8764- 4359. © AME Publishing Company. Transl Cancer Res 2025;14(12):9027-9052 | [https://dx.doi.org/10.21037/tcr-2025-1007](https://dx.doi.org/10.21037/tcr-

FAQs

What is the main purpose of this literature review?

To provide an updated summary of the current evidence, key challenges, and future directions for diagnosis, classification, and management of advanced and metastatic NSCLC with MET alterations.

Which MET alteration types are highlighted in the review?

The review focuses on MET exon 14 skipping (METex14), MET amplification (MET AMP), MET overexpression (MET OE), and MET fusion (MET FUS).

What treatment approaches does the review cover for MET-altered NSCLC?

It reviews established and actively investigated strategies including MET tyrosine kinase inhibitors, anti-MET and anti-HGF antibodies, bispecific antibodies, antibody-drug conjugates, and immunotherapy.

Sep 30, 2026

Upload by James