Preclinical Model of Organotypic Culture for Pharmacodynamic Profiling of Human Tumors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2010 Apr 21

PMID 20404174

Citations 143

Authors

Valentina Vaira

Giuseppe Fedele

Saumyadipta Pyne

Ester Fasoli

Giorgia Zadra

Dyane Bailey

Eric Snyder

Alice Faversani

Guido Coggi

Richard Flavin

Silvano Bosari

Massimo Loda

Affiliations

Soon will be listed here.

Abstract

Predicting drug response in cancer patients remains a major challenge in the clinic. We have perfected an ex vivo, reproducible, rapid and personalized culture method to investigate antitumoral pharmacological properties that preserves the original cancer microenvironment. Response to signal transduction inhibitors in cancer is determined not only by properties of the drug target but also by mutations in other signaling molecules and the tumor microenvironment. As a proof of concept, we, therefore, focused on the PI3K/Akt signaling pathway, because it plays a prominent role in cancer and its activity is affected by epithelial-stromal interactions. Our results show that this culture model preserves tissue 3D architecture, cell viability, pathway activity, and global gene-expression profiles up to 5 days ex vivo. In addition, we show pathway modulation in tumor cells resulting from pharmacologic intervention in ex vivo culture. This technology may have a significant impact on patient selection for clinical trials and in predicting response to small-molecule inhibitor therapy.

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