ArticleCancer research2015
Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 44 citations in OpenAlex.
- Review
- Macropinocytosis and Vascularization Determine Response to mTOR Inhibitors in Lung Squamous Cell Carcinoma.Cancer research · 2026Article
- TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes STK11-Mutant Tumors to Anti-PD-1 Immunotherapy.Cancer research · 2025Article
- A phase II trial of mTORC1/2 inhibition in STK11 deficient non small cell lung cancer.NPJ precision oncology · 2025Article
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- N-Myristoytransferase Inhibition Causes Mitochondrial Iron Overload and Parthanatos in TIM17A-Dependent Aggressive Lung Carcinoma.Cancer research communications · 2024Article
- Targeting Myc-driven stress addiction in colorectal cancer.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2023Review
- Article
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- LKB1: Can We Target an Hidden Target? Focus on NSCLC.Frontiers in oncology · 2022Review
- Metabolic Phenotypes, Dependencies, and Adaptation in Lung Cancer.Cold Spring Harbor perspectives in medicine · 2021Review
- Therapeutic Repurposing of Biguanides in Cancer.Trends in cancer · 2021Review
- Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy.Frontiers in oncology · 2021Review
- Shining a light on metabolic vulnerabilities in non-small cell lung cancer.Biochimica et biophysica acta. Reviews on cancer · 2021Review
- Repression of LKB1 byCell reports. Medicine · 2020Article
- Regulating T Cell Population Alleviates SLE by Inhibiting mTORC1/C2 in MRL/lpr Mice.Frontiers in pharmacology · 2020Article
- Hexokinase 2 Depletion Confers Sensitization to Metformin and Inhibits Glycolysis in Lung Squamous Cell Carcinoma.Frontiers in oncology · 2020Article
- Metabolic Rewiring in Response to Biguanides Is Mediated by mROS/HIF-1a in Malignant Lymphocytes.Cell reports · 2019Article
- Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy.Nature reviews. Cancer · 2019Review
- LKB1 and KEAP1/NRF2 Pathways Cooperatively Promote Metabolic Reprogramming with Enhanced Glutamine Dependence inCancer research · 2019Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Inactivation of the LKB1 tumor suppressor is a frequent event in non-small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1-mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1-mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1-mutant adenocarcinomas and squamous cell tumors.
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Registered trials
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 OpenQuestion graph.