Bortezomib sensitivity is tissue dependent and high expression of the 20S proteasome precludes good response in malignant pleural mesothelioma.

ABSTRACT:

Background

Bortezomib is an approved proteasome inhibitor for the treatment of certain lymphoma subtypes. Two clinical trials investigated bortezomib in patients with malignant pleural mesothelioma (MPM) and failed to improve outcome. We present a potential explanation for this event.

Methods

171 patients with MPM were analyzed for their mRNA expression of proteasomal subunits PSMA1, PSMA5, PSMB1, PSMB2, PSMB4 and PSMB5 via qPCR (n=84) or sequencing (n=87 TCGA/cBioPortal data set "Mesothelioma"). Outcome and subunit expression were correlated. Four mesothelial and one fibroblast cell line were treated with bortezomib and cisplatin. Cellular response was measured after 0, 6, 12, 24, 48 and 72 hrs. Enzyme activity of proteasomal subunits was assessed via function

SUBMITTER: Walter RFH 

PROVIDER: S-EPMC6765394 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature