Disruption of redox homeostasis for combinatorial drug efficacy in K-Ras tumors as revealed by metabolic connectivity profiling.

ABSTRACT:

Abstract

Background

Rewiring of metabolism induced by oncogenic K-Ras in cancer cells involves both glucose and glutamine utilization sustaining enhanced, unrestricted growth. The development of effective anti-cancer treatments targeting metabolism may be facilitated by the identification and rational combinatorial targeting of metabolic pathways.

Methods

We performed mass spectrometric metabolomics analysis in vitro and in vivo experiments to evaluate the efficacy of drugs and identify metabolic connectivity.

Results

We show that K-Ras-mutant lung and colon cancer cells exhibit a distinct metabolic rewiring, the latter being more dependent on respiration. Combined treatment with the glutaminase inhibitor CB-839 and the PI3K/aldolase inhibitor NV

SUBMITTER: Gaglio D 

PROVIDER: S-EPMC7523077 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature