MEK inhibition abrogates sunitinib resistance in a renal cell carcinoma patient-derived xenograft model.

ABSTRACT:

Background

Renal cell carcinoma (RCC) patients treated with tyrosine kinase inhibitors (TKI) typically respond initially, but usually develop resistance to therapy. We utilised transcriptome analysis to identify gene expression changes during development of sunitinib resistance in a RCC patient-derived xenograft (PDX) model.

Methods

RCC tumours were harvested during pre-treatment, response and escape phases. Direct anti-proliferative effects of sunitinib plus MEK inhibitor were assessed. Activation status (phosphorylation) of MEK1/2 and ERK1/2 was determined, myeloid-derived suppressor cells (MDSC) sub-fractions were quantitated and G-CSF was measured by ELISA.

Results

During the response phase, tumours exhibited 91% reduction in volume, characterised by decreased exp

SUBMITTER: Diaz-Montero CM 

PROVIDER: S-EPMC5061902 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature