Inhibition of ligand-independent constitutive activation of the Met oncogenic receptor by the engineered chemically-modified antibody DN30.

ABSTRACT: An awesome number of experimental and clinical evidences indicate that constitutive activation of the Met oncogenic receptor plays a critical role in the progression of cancer toward metastasis and/or resistance to targeted therapies. While mutations are rare, the common mechanism of Met activation is overexpression, either by gene amplification ('addiction') or transcriptional activation ('expedience'). In the first instance ligand-independent kinase activation plays a major role in sustaining the transformed phenotype. Anti-Met antibodies directed against the receptor binding site behave essentially as ligand (Hepatocyte Growth Factor, HGF) antagonists and are ineffective to counteract ligand-independent activation. The monovalent chimeric MvDN30 antibody fragment, PEGylated to extend it

SUBMITTER: Vigna E 

PROVIDER: S-EPMC5528712 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature