ArticleOncotarget2014
Pre-clinical study of drug combinations that reduce breast cancer burden due to aberrant mTOR and metabolism promoted by LKB1 loss.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 23 citations in OpenAlex.
- Breast cancer therapy: from the perspective of glucose metabolism and glycosylation.Molecular biology reports · 2024Review
- Targeting SMAD-Dependent Signaling: Considerations in Epithelial and Mesenchymal Solid Tumors.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Loss of chromosome 9p21 is associated with a poor prognosis in adenosquamous carcinoma of the pancreas.Precision clinical medicine · 2023Article
- Relationship between metabolic reprogramming and drug resistance in breast cancer.Frontiers in oncology · 2022Review
- The Tumor Suppressor Kinase LKB1: Metabolic Nexus.Frontiers in cell and developmental biology · 2022Review
- Single-cell RNA sequencing for the identification of early-stage lung cancer biomarkers from circulating blood.NPJ genomic medicine · 2021Article
- Review
- Review
- Everolimus versus alpelisib in advanced hormone receptor-positive HER2-negative breast cancer: targeting different nodes of the PI3K/AKT/mTORC1 pathway with different clinical implications.Breast cancer research : BCR · 2020Review
- An occult urothelial carcinoma with wide multiorgan metastases and its genetic alteration profiling: Case report and literature review.Medicine · 2019Review
- Review
- LKB1/AMPK Pathway and Drug Response in Cancer: A Therapeutic Perspective.Oxidative medicine and cellular longevity · 2019Review
- Raptor mediates the antiproliferation of cardamonin by mTORC1 inhibition in SKOV3 cells.OncoTargets and therapy · 2018Article
- Article
- Functional characterization of AMP-activated protein kinase signaling in tumorigenesis.Biochimica et biophysica acta · 2016Review
- SCD1 is associated with tumor promotion, late stage and poor survival in lung adenocarcinoma.Oncotarget · 2016Article
- Clinical Relevance of Liver Kinase B1(LKB1) Protein and Gene Expression in Breast Cancer.Scientific reports · 2016Article
- Heightening Energetic Stress Selectively Targets LKB1-Deficient Non-Small Cell Lung Cancers.Cancer research · 2015Article
- Computational Inferences of the Functions of Alternative/Noncanonical Splice Isoforms Specific to HER2+/ER-/PR- Breast Cancers, a Chromosome 17 C-HPP Study.Journal of proteome research · 2015Article
- Targeting LKB1 in cancer - exposing and exploiting vulnerabilities.British journal of cancer · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Cancer therapies that simultaneously target activated mammalian target of rapamycin (mTOR) and cell metabolism are urgently needed. The goal of our study was to identify therapies that effectively inhibited both mTOR activity and cancer cell metabolism in primary tumors in vivo. Using our mouse model of spontaneous breast cancer promoted by loss of LKB1 expression in an ErbB2 activated model; referred to as LKB1-/-NIC mice, we evaluated the effect of novel therapies in vivo on primary tumors. Treatment of LKB1-/-NIC mice with AZD8055 and 2-DG mono-therapies significantly reduced mammary gland tumorigenesis by inhibiting mTOR pathways and glycolytic metabolism; however simultaneous inhibition of these pathways with AZD8055/2-DG combination was significantly more effective at reducing tumor volume and burden. At the molecular level, combination treatment inhibited mTORC1/mTORC2 activity, selectively inhibited mitochondria function and blocked MAPK pro-survival signaling responsible for the ERK-p90RSK feedback loop. Our findings suggest that loss of LKB1 expression be considered a marker for metabolic dysfunction given its role in regulating AMPK and mTOR function. Finally, the outcome of our pre-clinical study confirms therapies that simultaneously target mTORC1/mTORC2 and glycolytic metabolism in cancer produce the best therapeutic outcome for the treatment of patients harboring metabolically active HER2 positive breast cancers.
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What OpenQuestion holds
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.