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 () 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 () mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies. 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. 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. 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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http://dx.doi.org/10.3390/antib13040088 | DOI Listing |
Pharmaceuticals (Basel)
November 2024
Department of Oncology, University of Turin, Regione Gonzole 10, 10143 Orbassano, Italy.
The MET receptor, commonly known as HGF (hepatocyte growth factor) receptor, is a focus of extensive scientific research. MET has been linked to embryonic development, tissue regeneration following injury, tumorigenesis, and cancer metastasis. These functions underscore its involvement in numerous cellular processes, including stemness, proliferation, motility, cell dissociation, and survival.
View Article and Find Full Text PDFAntibodies (Basel)
October 2024
Department of Medicine, Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA.
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 () 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 () mutations. This review examines the development and clinical efficacy of anti-MET antibody therapies.
View Article and Find Full Text PDFPLoS One
April 2024
Biotechnology Discovery Research, Lilly Technology Center North, Indianapolis, IN, United States of America.
Many oncology antibody-drug conjugates (ADCs) have failed to demonstrate efficacy in clinic because of dose-limiting toxicity caused by uptake into healthy tissues. We developed an approach that harnesses ADC affinity to broaden the therapeutic index (TI) using two anti-mesenchymal-epithelial transition factor (MET) monoclonal antibodies (mAbs) with high affinity (HAV) or low affinity (LAV) conjugated to monomethyl auristatin E (MMAE). The estimated TI for LAV-ADC was at least 3 times greater than the HAV-ADC.
View Article and Find Full Text PDFInvest New Drugs
April 2023
Recombinant Proteins Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran.
The usage of monoclonal antibodies (mAbs) and antibody fragments, as a matter associated with the biopharmaceutical industry, is increasingly growing. Harmonious with this concept, we designed an exclusive modeled single-chain variable fragment (scFv) against mesenchymal-epithelial transition (MET) oncoprotein. This scFv was newly developed from Onartuzumab sequence by gene cloning, and expression using bacterial host.
View Article and Find Full Text PDFLung Cancer
November 2022
Thorax Institute Curie Montsouris, Institut Curie, Paris, France; UVSQ, Paris Saclay University, Versailles, France. Electronic address:
Contexte: The Epidermal Growth Factor Receptor (EGFR) is mutated in 10-15% of patients with lung adenocarcinoma. At metastatic stage EGFR tyrosine kinase inhibitors (TKIs) are used front line for patients harboring targetable mutations. Novel anti-EGFR therapies are being developed.
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