ArticleOncotarget2016
Different metabolic responses to PI3K inhibition in NSCLC cells harboring wild-type and G12C mutant KRAS.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- NSCLC Cells Resistance to PI3K/mTOR Inhibitors Is Mediated by Delta-6 Fatty Acid Desaturase (FADS2).Cells · 2022Article
- The Tumor Suppressor Kinase LKB1: Metabolic Nexus.Frontiers in cell and developmental biology · 2022Review
- Characterization With KRAS Mutant Is a Critical Determinant in Immunotherapy and Other Multiple Therapies for Non-Small Cell Lung Cancer.Frontiers in oncology · 2021Review
- Shining a light on metabolic vulnerabilities in non-small cell lung cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Mitochondrial structural alterations in ovarian cancer patient-derived xenografts resistant to cisplatin.American journal of cancer research · 2021Article
- TargetingJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Article
- Article
- Activity of Birinapant, a SMAC Mimetic Compound, Alone or in Combination in NSCLCs With Different Mutations.Frontiers in oncology · 2020Article
- Biomarkers in Lung Cancer Screening: Achievements, Promises, and Challenges.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2019Review
- Co-occurring KRAS mutation/LKB1 loss in non-small cell lung cancer cells results in enhanced metabolic activity susceptible to caloric restriction: an in vitro integrated multilevel approach.Journal of experimental & clinical cancer research : CR · 2018Article
- Engineered microfluidic bioreactor for examining the three-dimensional breast tumor microenvironment.Biomicrofluidics · 2018Article
- Next-generation metabolomics in lung cancer diagnosis, treatment and precision medicine: mini review.Oncotarget · 2017Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
KRAS mutations in non-small-cell lung cancer (NSCLC) patients are considered a negative predictive factor and indicate poor response to anticancer treatments. KRAS mutations lead to activation of the PI3K/akt/mTOR pathway, whose inhibition remains a challenging clinical target. Since the PI3K/akt/mTOR pathway and KRAS oncogene mutations all have roles in cancer cell metabolism, we investigated whether the activity of PI3K/akt/mTOR inhibitors (BEZ235 and BKM120) in cells harboring different KRAS status is related to their metabolic effect. Isogenic NSCLC cell clones expressing wild-type (WT) and mutated (G12C) KRAS were used to determine the response to BEZ235 and BKM120. Metabolomics analysis indicated the impairment of glutamine in KRAS-G12C and serine metabolism in KRAS-WT, after pharmacological blockade of the PI3K signaling, although the net effect on cell growth, cell cycle distribution and caspase activation was similar. PI3K inhibitors caused autophagy in KRAS-WT, but not in KRAS-G12C, where there was a striking decrease in ammonia production, probably a consequence of glutamine metabolism impairment.These findings lay the grounds for more effective therapeutic combinations possibly distinguishing wild-type and mutated KRAS cancer cells in NSCLC, exploiting their different metabolic responses to PI3K/akt/mTOR inhibitors.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.