Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer. (April 2021)

• Record Type: Journal Article
• Authors: Moosavi, Fatemeh; Giovannetti, Elisa; Peters, Godefridus J.; Firuzi, Omidreza
• Is Part Of: Critical reviews in oncology/hematology. Volume 160(2021)
• Publication Date: 2021-04
• Subjects: ABC adenosine triphosphate (ATP)-binding cassette -- ADAM a disintegrin and metalloproteinase domain containig protein -- BCRP breast cancer resistance protein -- CAF cancer-associated fibroblast -- CDA cytidine deaminase -- Chk1 serine/threonine-specific protein kinase -- CI confidence interval -- CNG copy number gain -- CSC cancer stem cell -- DCR disease control rate -- DDA DNA damaging agent -- DDR DNA damage response -- EGFR epithelial growth factor receptor -- FAK focal adhesion kinase -- FDA Food and drug administration -- FISH fluorescence in situ hybridization -- GaB1 GrB2-associated binding protein -- GBM glioblastoma multiforme -- GrB2 growth factor receptor- bound protein 2 -- HCC hepatocellular carcinoma -- HGF hepatocyte growth factor -- HIF hypoxia-inducible factor -- HR hazard ratio -- IGF-1R insulin-like growth factor 1 receptor -- IHC immunohistochemistry -- MDR multidrug resistance -- MET mesenchymal-epithelial transition tyrosine kinase receptor, c-MET -- Metex14 mutations MET exon 14 skipping mutations -- NSCLC non-small cell lung cancer -- ORR overall response rate -- OS overall survival -- PARP poly (ADP-ribose) polymerase -- PD-L1 programmed cell death ligand 1 -- PDX patient-derived xenograft -- PFS progression free survival -- P-gp P-glycoprotein -- PI3K phosphoinositide 3-kinase -- PRCC papillary renal cell carcinoma -- PSC pancreatic stellate cell -- RCC renal cell carcinoma -- ROS reactive oxygen species -- RTK receptor tyrosine kinase -- STAT3 signal transducer and activator of transcription 3 -- TGF-α transforming growth factor-α -- TKI tyrosine kinase inhibitor -- TME tumor microenvironment -- TRAIL tumor necrosis factor-related apoptosis-inducing ligand -- VEGFR vascular endothelial growth factor receptor; c-MET -- Receptor tyrosine kinase -- DNA damage response -- Multidrug resistance -- Combination therapy -- Cancer stem cells -- Tumor microenvironment -- Immunotherapy; Oncology -- Periodicals; Hematology -- Periodicals; 616.994
• DOI: 10.1016/j.critrevonc.2021.103234
• Languages: English
• ISSNs: 1040-8428

Abstract

Highlights: Dysregulation of HGF/MET pathway is involved in tumorigenesis and drug resistance. Anti-HGF/MET agents are often combined with targeted or cytotoxic agents. Preclinical and clinical evidence of successful combinations are reviewed. Biomarkers are essential in selection of beneficial combinations. Abstract: MET receptor has emerged as a druggable target across several human cancers. Agents targeting MET and its ligand hepatocyte growth factor (HGF) including small molecules such as crizotinib, tivantinib and cabozantinib or antibodies including rilotumumab and onartuzumab have proven their values in different tumors. Recently, capmatinib was approved for treatment of metastatic lung cancer with MET exon 14 skipping. In this review, we critically examine the current evidence on how HGF/MET combination therapies may take advantage of synergistic effects, overcome primary or acquired drug resistance, target tumor microenvironment, modulate drug metabolism or tackle pharmacokinetic issues. Preclinical and clinical studies on the combination of HGF/MET-targeted agents with conventional chemotherapeutics or molecularly targeted treatments (including EGFR, VEGFR, HER2, RAF/MEK, and PI3K/Akt targeting agents) and also the value of biomarkers are examined. Our deeper understanding of molecular mechanisms underlying successful pharmacological combinations is crucial to find the best personalized treatment regimens for cancer patients.