TY - JOUR
T1 - Combination of HGF/MET-targeting agents and other therapeutic strategies in cancer
AU - Moosavi, Fatemeh
AU - Giovannetti, Elisa
AU - Peters, Godefridus J.
AU - Firuzi, Omidreza
N1 - Funding Information:
The authors wish to thank the support of the National Institute for Medical Research Development (NIMAD), Tehran, Iran (Grant number:957652).NWO Visitor's Travel grant (number040.11.609) to O.F. andCCA Foundation and AIRC grants to E.G. are also appreciated. We also would like to thank the Vice-Chancellor for Research, Shiraz University of Medical Sciences (Grant number: 1396-01-106-15688) for postdoctoral grant to F.M.
Funding Information:
The authors wish to thank the support of the National Institute for Medical Research Development (NIMAD), Tehran, Iran (Grant number: 957652). NWO Visitor's Travel grant (number 040.11.609) to O.F. and CCA Foundation and AIRC grants to E.G. are also appreciated. We also would like to thank the Vice-Chancellor for Research, S hiraz University of Medical Sciences (Grant number: 1396-01-106-15688 ) for postdoctoral grant to F.M.
Publisher Copyright:
© 2021 Elsevier B.V.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/4/1
Y1 - 2021/4/1
N2 - 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.
AB - 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.
KW - Cancer stem cells
KW - Combination therapy
KW - DNA damage response
KW - Immunotherapy
KW - Multidrug resistance
KW - Receptor tyrosine kinase
KW - Tumor microenvironment
KW - c-MET
UR - http://www.scopus.com/inward/record.url?scp=85101390327&partnerID=8YFLogxK
U2 - 10.1016/j.critrevonc.2021.103234
DO - 10.1016/j.critrevonc.2021.103234
M3 - Review article
C2 - 33497758
VL - 160
JO - Critical Reviews in Oncology / Hematology
JF - Critical Reviews in Oncology / Hematology
SN - 1040-8428
M1 - 103234
ER -