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Background  Advanced non-small cell lung cancer (NSCLC) is an aggressive tumor that is treated with a combination of chemotherapy and radiation if the patient is not a candidate for surgery. Predictive biomarkers for response to radiotherapy are lacking in this patient population, making it a non-tailored therapy regimen with unknown outcome. Twenty to 30 % of NSCLC harbor an activating mutation in  KRAS  that may confer radioresistance. We hypothesized that mutant  KRAS  can regulate glutamine metabolism genes in NSCLC and maintain tumor redox balance through transamination reactions that generate cytosolic NADPH via malic enzyme 1 ( ME1 ), which may contribute to radioresistance.    Findings  A doxycycline-inducible mouse model of  KRAS   G12D   driven NSCLC and patient data was analyzed from multiple publicly accessible databases including TCGA, CCLE, NCBI GEO and Project Achilles.  ME1  expression was found to be mutant  KRAS  associated in both a NSCLC mouse model and human NSCLC cancer cell lines. Perturbing glutamine metabolism sensitized mutant  KRAS , but not wild-type  KRAS  NSCLC cell lines to radiation treatment. NSCLC survival analysis revealed that patients with elevated  ME1  and  GOT1  expression had significantly worse outcomes after radiotherapy, but this was not seen after chemotherapy alone.    Conclusions   KRAS  driven glutamine metabolism genes, specifically  ME1  and  GOT1  reactions, may be a predictive marker and potential therapeutic target for radiotherapy in NSCLC.    Electronic supplementary material  The online version of this article (doi:10.1186/s13014-015-0457-x) contains supplementary material, which is available to authorized users.

Mutant KRAS associated malic enzyme 1 expression is a predictive marker for radiation therapy response in non-small cell lung cancer