2. Academic Validation
  3. MET Alterations in Cancer and MET-Targeted Therapy: Detection Strategies, Treatment Efficacy, and Emerging Technologies

MET Alterations in Cancer and MET-Targeted Therapy: Detection Strategies, Treatment Efficacy, and Emerging Technologies

  • Target Oncol. 2025 Sep;20(5):767-789. doi: 10.1007/s11523-025-01166-0.
Jieun Park 1,  Chaithanya Chelakkot 1,  Ji-Hye Nam 2,  Hun Seok Lee 3,  Chae Rin Kim 4,  Yeonwoo Lee 5,  Mi-Sook Lee 6,  Yoon-La Choi 7 8 9,  Young Kee Shin 10 11 12 13
Affiliations

Affiliations

  • 1 Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea.
  • 2 Central Research Institute, Logone Bio-Convergence Research Foundation, Seoul, Republic of Korea.
  • 3 Cichlid Corporation, Seoul, Republic of Korea.
  • 4 Abion Inc, Seoul, Republic of Korea.
  • 5 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
  • 6 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea.
  • 7 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Republic of Korea. [email protected].
  • 8 Laboratory of Molecular Pathology and Theranostics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. [email protected].
  • 9 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. [email protected].
  • 10 Research Institute of Pharmaceutical Science, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. [email protected].
  • 11 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea. [email protected].
  • 12 Laboratory of Molecular Pathology and Cancer Genomics, College of Pharmacy, Seoul National University, Seoul, Republic of Korea. [email protected].
  • 13 Future Innovation research Institute, Seoul National University Siheung campus, Seoul, Republic of Korea. [email protected].
PMID: 40679792 DOI: 10.1007/s11523-025-01166-0
Abstract

The MET signaling pathway is dysregulated in several cancers through various mechanisms, including gene mutations, amplifications, rearrangements, and protein overexpression. MET inhibitors have demonstrated clinical benefits in solid tumors including non-small-cell lung Cancer (NSCLC), highlighting the importance of optimizing MET alteration detection methods and cut-off values to enhance the efficacy of MET-targeted therapies and improve patient outcomes. Research on MET alterations has primarily focused on MET exon 14 skipping mutations, MET amplification, and MET overexpression. This review summarizes the frequency of MET alterations across different Cancer types and the clinical validation of MET alterations in MET-targeted therapies, offering a detailed comparison of objective response rates (ORR) for therapies including crizotinib, capmatinib, tepotinib, savolitinib, telisotuzumab vedotin, telisotuzumab adizutecan, and amivantamab. The review also addresses the challenges in detecting MET exon 14 skipping mutations, such as issues with false positives and negatives, and underscores the need for standardization in MET amplification detection. Trials vary in their cut-offs for MET gene copy number (GCN) and MET/CEP7 ratio and MET expression detection methods, leading to inconsistencies in detection. Additionally, emerging technologies such as circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) analyses have been investigated for their potential to improve MET alterations detection. This review also highlights studies that demonstrate the potential of MET ctDNA and CTC analyses to predict treatment responses and identify resistance mechanisms in MET-targeted therapies.

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