ArticleOncotarget2015
Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 41 citations in OpenAlex.
- Current Insights and Future Directions of Multiomic and Spatial-Omic Analysis in Non-Small Cell Lung Cancer.JCO precision oncology · 2026Review
- Refining treatment strategies for non-small cell lung cancer lacking actionable mutations: insights from multi-omics studies.British journal of cancer · 2025Review
- Mapping three-dimensional intratumor proteomic heterogeneity in uterine serous carcinoma by multiregion microsampling.Clinical proteomics · 2024Article
- RHOAScience signaling · 2023Article
- Functional and biological heterogeneity of KRASScience signaling · 2022Article
- PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine.Journal for immunotherapy of cancer · 2021Article
- Article
- Integrated multi-omics analyses on patient-derived CRC organoids highlight altered molecular pathways in colorectal cancer progression involving PTEN.Journal of experimental & clinical cancer research : CR · 2021Article
- The KRASMolecular cancer therapeutics · 2021Article
- Neratinib-Plus-Cetuximab in Quadruple-WT (Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Heterogeneous Off-Target Effects of Ultra-Low Dose Dimethyl Sulfoxide (DMSO) on Targetable Signaling Events in Lung Cancer In Vitro Models.International journal of molecular sciences · 2021Article
- Low-Dose Vertical Inhibition of the RAF-MEK-ERK Cascade Causes Apoptotic Death of KRAS Mutant Cancers.Cell reports · 2020Article
- The KRASCancer discovery · 2020Article
- Atypical KRASCancer discovery · 2020Article
- Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer.Nature medicine · 2019Article
- Article
- A pilot study exploring the molecular architecture of the tumor microenvironment in human prostate cancer using laser capture microdissection and reverse phase protein microarray.Molecular oncology · 2016Article
- Activation of MEK1/2-ERK1/2 signaling during NNK-induced lung carcinogenesis in female A/J mice.Cancer medicine · 2016Article
- Inhibition of Akt Enhances the Chemopreventive Effects of Topical Rapamycin in Mouse Skin.Cancer prevention research (Philadelphia, Pa.) · 2016Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Little is known about the complex signaling architecture of KRAS and the interconnected RAS-driven protein-protein interactions, especially as it occurs in human clinical specimens. This study explored the activated and interconnected signaling network of KRAS mutant lung adenocarcinomas (AD) to identify novel therapeutic targets.Thirty-four KRAS mutant (MT) and twenty-four KRAS wild-type (WT) frozen biospecimens were obtained from surgically treated lung ADs. Samples were subjected to Laser Capture Microdissection and Reverse Phase Protein Microarray analysis to explore the expression/activation levels of 150 signaling proteins along with co-activation concordance mapping. An independent set of 90 non-small cell lung cancers (NSCLC) was used to validate selected findings by immunohistochemistry (IHC).Compared to KRAS WT tumors, the signaling architecture of KRAS MT ADs revealed significant interactions between KRAS downstream substrates, the AKT/mTOR pathway, and a number of Receptor Tyrosine Kinases (RTK). Approximately one-third of the KRAS MT tumors had ERK activation greater than the WT counterpart (p<0.01). Notably 18% of the KRAS MT tumors had elevated activation of the Estrogen Receptor alpha (ER-α) (p=0.02).This finding was verified in an independent population by IHC (p=0.03).KRAS MT lung ADs appear to have a more intricate RAS linked signaling network than WT tumors with linkage to many RTKs and to the AKT-mTOR pathway. Combination therapy targeting different nodes of this network may be necessary to treat this group of patients. In addition, for patients with KRAS MT tumors and activation of the ER-α, anti-estrogen therapy may have important clinical implications.
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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 OpenQuestion graph.