Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions

<b>Background/Objectives:</b> Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal–epithelial transition (<i>MET</i>) gene plays a significant role in N...

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Main Authors: Kinsley Wang, Robert Hsu
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Antibodies
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Online Access:https://www.mdpi.com/2073-4468/13/4/88
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author Kinsley Wang
Robert Hsu
author_facet Kinsley Wang
Robert Hsu
author_sort Kinsley Wang
collection DOAJ
description <b>Background/Objectives:</b> Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal–epithelial transition (<i>MET</i>) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (<i>EGFR</i>) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. <b>Methods:</b> A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. <b>Results:</b> Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. <b>Conclusions:</b> MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.
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spelling doaj-art-c392bd046b8b447a8a67f2ddc1e42ecf2025-08-20T02:00:52ZengMDPI AGAntibodies2073-44682024-10-011348810.3390/antib13040088Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future DirectionsKinsley Wang0Robert Hsu1Department of Medicine, University of Arizona College of Medicine—Phoenix, Phoenix, AZ 85004, USADepartment of Medicine, Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA<b>Background/Objectives:</b> Non-small-cell lung cancer (NSCLC) remains a leading cause of cancer mortality globally, though advances in targeted therapies have improved treatment outcomes. The mesenchymal–epithelial transition (<i>MET</i>) gene plays a significant role in NSCLC, often through protein overexpression, exon 14 skipping mutations, and gene amplification, many of which arise as resistance mechanisms to other oncogenic drivers like epidermal growth factor receptor (<i>EGFR</i>) mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. <b>Methods:</b> A comprehensive literature search was conducted using major medical databases looking at key relevant studies on anti-MET antibody studies. Both authors reviewed the literature, assessed study quality, and interpreted the results from each study. <b>Results:</b> Amivantamab, a bispecific EGFR/MET antibody was approved to treat EGFR exon 20 insertion and now has recently been extended to target classical EGFR mutations with progression on osimertinib. Other important anti-MET targeted therapies in development include antibody drug conjugates such as telisotuzumab vedotin, REGN5093-M114, and AZD9592 and emibetuzumab, which is a humanized immunoglobulin G4 monoclonal bivalent MET antibody. <b>Conclusions:</b> MET plays a significant role in NSCLC and amivantamab along with other anti-MET targeted therapies play a role in directly targeting MET and addressing acquired resistance to oncogenic drivers. Future research should focus on developing novel MET antibody drugs and exploring new therapeutic combinations to enhance treatment efficacy and overcome resistance in NSCLC. Refining biomarker-driven approaches to ensure precise patient selection is also critical to optimizing treatment outcomes.https://www.mdpi.com/2073-4468/13/4/88MET (mesenchymal–epithelial transition factor)NSCLC (non-small-cell lung cancer)EGFR-mutated NSCLCtargeted therapiesamivantamab
spellingShingle Kinsley Wang
Robert Hsu
Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
Antibodies
MET (mesenchymal–epithelial transition factor)
NSCLC (non-small-cell lung cancer)
EGFR-mutated NSCLC
targeted therapies
amivantamab
title Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
title_full Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
title_fullStr Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
title_full_unstemmed Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
title_short Anti-MET Antibody Therapies in Non-Small-Cell Lung Cancer: Current Progress and Future Directions
title_sort anti met antibody therapies in non small cell lung cancer current progress and future directions
topic MET (mesenchymal–epithelial transition factor)
NSCLC (non-small-cell lung cancer)
EGFR-mutated NSCLC
targeted therapies
amivantamab
url https://www.mdpi.com/2073-4468/13/4/88
work_keys_str_mv AT kinsleywang antimetantibodytherapiesinnonsmallcelllungcancercurrentprogressandfuturedirections
AT roberthsu antimetantibodytherapiesinnonsmallcelllungcancercurrentprogressandfuturedirections