Proteasome stress sensitizes malignant pleural mesothelioma cells to bortezomib-induced apoptosis.

ABSTRACT: Based on promising results in preclinical models, clinical trials have been performed to evaluate the efficacy of the first-in-class proteasome inhibitor bortezomib towards malignant pleural mesothelioma (MPM), an aggressive cancer arising from the mesothelium of the serous cavities following exposure to asbestos. Unexpectedly, only minimal therapeutic benefits were observed, thus implicating that MPM harbors inherent resistance mechanisms. Identifying the molecular bases of this primary resistance is crucial to develop novel pharmacologic strategies aimed at increasing the vulnerability of MPM to bortezomib. Therefore, we assessed a panel of four human MPM lines with different sensitivity to bortezomib, for functional proteasome activity and levels of free and polymerized ubiquitin. We fo

SUBMITTER: Cerruti F 

PROVIDER: S-EPMC5732203 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature