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 geneexpression 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.
Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors / V. Vaira, G. Fedele, S. Pyne, E. Fasoli, G. Zadra, D. Bailey, E. Snyder, A. Faversani, G. Coggi, R. Flavin, S. Bosari, M. Loda, A. Faversani, E. Fasoli. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 107:18(2010 May), pp. 8352-8356.
|Titolo:||Preclinical model of organotypic culture for pharmacodynamic profiling of human tumors|
VAIRA, VALENTINA (Primo)
BOSARI, SILVANO (Penultimo)
LODA, MASSIMILIANO (Ultimo)
|Settore Scientifico Disciplinare:||Settore MED/08 - Anatomia Patologica|
|Data di pubblicazione:||mag-2010|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1073/pnas.0907676107|
|Appare nelle tipologie:||01 - Articolo su periodico|