Therapeutic evaluation of monoclonal antibody-maytansinoid conjugate as a model of RON-targeted drug delivery for pancreatic cancer treatment.

ABSTRACT: Aberrant expression of the RON receptor tyrosine kinase, a member of the MET proto-oncogene family, contributes significantly to pancreatic cancer tumorigenesis and chemoresistance. Here we validate RON as a target for pancreatic cancer therapy using a novel anti-RON antibody Zt/g4-drug maytansinoid conjugates (Zt/g4-DM1) as a model for RON-targeted drug delivery to kill pancreatic cancer cells. In pancreatic cancer cell lines overexpressing RON, Zt/g4-DM1 rapidly induced receptor endocytosis, arrested cell cycle at G2/M phase, reduced cell viability, and subsequently caused massive cell death. These in vitro observations help to establish a correlation between the number of the cell surface RON receptors and the efficacy of Zt/g4-DM1 in reduction of cell viability. In mice, Zt/g4-DM1 phar

SUBMITTER: Yao HP 

PROVIDER: S-EPMC4889711 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature