Activity of the monocarboxylate transporter 1 inhibitor AZD3965 in small cell lung cancer.

ABSTRACT:

Purpose

The monocarboxylate transporter 1 (MCT1) inhibitor, AZD3965, is undergoing phase I evaluation in the United Kingdom. AZD3965 is proposed, via lactate transport modulation, to kill tumor cells reliant on glycolysis. We investigated the therapeutic potential of AZD3965 in small cell lung cancer (SCLC) seeking rationale for clinical testing in this disease and putative predictive biomarkers for trial use.

Experimental design

AZD3965 sensitivity was determined for seven SCLC cell lines, in normoxia and hypoxia, and for a tumor xenograft model. Proof of mechanism was sought via changes in intracellular/tumor lactate. Expression of MCT1 and related transporter MCT4 was assessed by Western blot analysis. Drug resistance was investigated via MCT4 siRNAi and overexpression. T

SUBMITTER: Polanski R 

PROVIDER: S-EPMC3929348 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature