Tumor Priming by SMO Inhibition Enhances Antibody Delivery and Efficacy in a Pancreatic Ductal Adenocarcinoma Model.

ABSTRACT: Despite frequent overexpression of numerous growth factor receptors by pancreatic ductal adenocarcinomas (PDAC), such as EGFR, therapeutic antibodies have not proven effective. Desmoplasia, hypovascularity, and hypoperfusion create a functional drug delivery barrier that contributes to treatment resistance. Drug combinations that target tumor/stroma interactions could enhance tumor deposition of therapeutic antibodies, although clinical trials have yet to support this strategy. We hypothesize that macromolecular or nanoparticulate therapeutic agents may best exploit stroma-targeting "tumor priming" strategies, based on the fundamental principles of the Enhanced Permeability and Retention phenomenon. Therefore, we investigated the molecular and pharmacologic tumor responses to NVP-LDE225, a

SUBMITTER: Wang J 

PROVIDER: S-EPMC6995668 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature