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| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Chakrabarti, Gaurab |
| Abstract | 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. |
| Related Links | https://ro-journal.biomedcentral.com/counter/pdf/10.1186/s13014-015-0457-x.pdf |
| Ending Page | 7 |
| Page Count | 7 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| DOI | 10.1186/s13014-015-0457-x |
| Journal | Radiation Oncology |
| Issue Number | 1 |
| Volume Number | 10 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-07-16 |
| Access Restriction | Open |
| Subject Keyword | Cancer Research Oncology Radiotherapy Imaging Radiology KRAS ME1 GOT1 Radioresistance Glutamine NSCLC ROS |
| Content Type | Text |
| Resource Type | Article |
| Subject | Radiology, Nuclear Medicine and Imaging Oncology |
| Journal Impact Factor | 3.3/2023 |
| 5-Year Journal Impact Factor | 3.6/2023 |
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