ArticleCancer cell2017
A Pan-Cancer Proteogenomic Atlas of PI3K/AKT/mTOR Pathway Alterations.
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Article in Cancer cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 357 papers.
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357citing papers in PubMed
24.6field-weighted citation impact, top 1% of its field
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Who cites it
357 citing papers in PubMed, 652 citations in OpenAlex.
- AKT mutant allele-specific activation dictates pharmacologic sensitivities.Nature communications · 2022Trial
- Dysregulated AKT signaling reprograms osteosarcoma to drive selective reliance on EP300.The Journal of experimental medicine · 2026Article
- Interpreting human genetic variation at atomic resolution.Nature genetics · 2026Review
- Deciphering the Medicinal Chemistry Aspects of Akt Inhibitors for the Management of Cancer: Structure-Activity Relationship Frameworks, Landscapes, and Optimization Approaches.Chemistry & biodiversity · 2026Review
- TET1-mediated DNA demethylation and transcription activation of MRPS17 induces lung adenocarcinoma through PI3K-AKT-mTOR pathway.Journal of molecular histology · 2026Article
- Single-Cell Analysis Reveals STARD10 as a Fatty Acid Metabolism Regulator of Breast Cancer Progression via the PI3K/Akt Pathway.International journal of molecular sciences · 2026Article
- Inference of upstream-mutation and metabolomic-signature causality identifies prognostic biomarkers and therapeutic targets in pancreatic cancer.Nature communications · 2026Article
- Inferring signaling pathway abnormalities from histopathological images via logic-constrained gene-pathway heterogeneous knowledge graph.npj biomedical innovations · 2026Article
- The Role of Protein Kinases in the Management of Oncological Diseases by Acting on Ferroptotic Pathways.International journal of molecular sciences · 2026Review
- Deciphering molecular pathways in urological cancers: A gateway to precision therapeutics.Journal of advanced research · 2026Review
- GPR176 enhances the epithelial‑mesenchymal transition in gastric cancer cells by activating the PI3K/AKT/mTOR signaling pathway.Oncology reports · 2026Article
- AI-Guided Discovery of Oncogenic Signaling Crosstalk in Tumor Progression and Drug Resistance.Oncology research · 2026Review
- Modulation of the PI3K/Akt signaling pathway by steroidal saponins: therapeutic implications in cancer.Frontiers in pharmacology · 2026Review
- Phase separation of p85β modulates hepatocellular carcinoma progression through POLR1A.International journal of biological sciences · 2026Article
- Genomic landscape of pediatric germ cell tumors reveals oncogenic mutations and copy number alterations.Frontiers in oncology · 2026Article
- Conventional and alternative approaches for targeting PIK3CA and PTEN alterations in head and neck, breast, and other cancers.Advances in biological regulation · 2026Review
- The mechanism of the PI3K-AKT-mTOR signaling pathway in renal cell carcinoma: current developments and future prospects.Frontiers in oncology · 2026Review
- Pan-cancer analysis reveals the prognostic and therapeutic relevance of MEX3A with a focus on chromophobe renal cell carcinoma.Frontiers in oncology · 2026Article
- Multiple Testing of Mix-and-Match Feature Sets in Multi-Omics.Statistics in medicine · 2026Article
- Phosphoinositide-dependent kinase 1 (PDK1) in cancer: molecular insights and therapeutic strategies.Frontiers in chemistry · 2026Review
297 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
42 authors at 10 institutions in 2 countries.
Yiqun ZhangDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Patrick Kwok-Shing NgDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Melanie KucherlapatiDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Fengju ChenDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Yuexin LiuDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yiu Huen TsangDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Guillermo de VelascoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medical Oncology, University Hospital 12 de Octubre, Madrid 28041, Spain.
Kang Jin JeongDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Rehan AkbaniDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Angela HadjipanayisDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Angeliki PantaziDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; KEW Inc., Cambridge, MA 02139, USA.
Christopher A BristowDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Eunjung LeeDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Harshad S MahadeshwarDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jiabin TangDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jianhua ZhangDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Lixing YangCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Sahil SethDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Semin LeeCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Xiaojia RenDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; KEW Inc., Cambridge, MA 02139, USA.
Xingzhi SongDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Huandong SunDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Jonathan SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Lovelace J LuquetteCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Ruibin XiCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Lynda ChinDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University Cambridge, Cambridge, MA 02142, USA.
Alexei ProtopopovDepartment of Genomic Medicine, Institute for Applied Cancer Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; KEW Inc., Cambridge, MA 02139, USA.
Thomas F WestbrookDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Biochemistry & Molecular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Carl Simon ShelleyDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA.
Toni K ChoueiriDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Michael IttmannDepartment of Pathology & Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Carter Van WaesTumor Biology Section, Head and Neck Surgery Branch, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, MD 20892, USA.
John N WeinsteinDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Han LiangDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA.
Elizabeth P HenskeThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02142, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
Andrew K GodwinDepartment of Pathology & Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Peter J ParkCenter for Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Raju KucherlapatiDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kenneth L ScottDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Gordon B MillsDepartment of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA. Electronic address: gmills@mdanderson.org.
David J KwiatkowskiThe Eli and Edythe L. Broad Institute of Massachusetts Institute of Technology, Harvard University, Cambridge, MA 02142, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA. Electronic address: dkwiatkowski@rics.bwh.harvard.edu.
Chad J CreightonDan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: creighto@bcm.edu.
The University of Texas MD Anderson Cancer Center · USHarvard University · USBaylor College of Medicine · USCenter for Systems Biology · USBrigham and Women's Hospital · USDana-Farber Cancer Institute · USMassachusetts Institute of Technology · USNational Institute on Deafness and Other Communication Disorders · USUniversity of Kansas Medical Center · USUniversity of Wisconsin–Madison · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI DAVID R ROWLEY · 2007 to 2026
$73.9MTreating the P13-Kinase/AKTP50CA101942 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Wanling Xie · 2003 to 2026
$53.4MTuberous Sclerosis-Pathway and PathogenesisP01CA120964 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI David J. Kwiatkowski · 2007 to 2026
$35.9MTargeting the PI3K Signaling Pathway in Endometrial CarcinomaP50CA098258 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BODURKA, DIANE · 2003 to 2020
$32.0MGenomics and Proteomics of Head and Neck CancerZIADC000074 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$11.1MIntegrative Pipeline for Analysis & Translational Application of TCGA Data (GDAC)U24CA143883 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKBANI, REHAN, MILLS, GORDON B. · 2009 to 2016
$10.6MNF-kappaB in pathogenesis and therapy of head and neck cancerZIADC000016 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.3MSignal and Transcription Factor Network interactions in Head and Neck CancerZIADC000073 · NIDCD · NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS · PI VAN WAES, CARTER · 2009 to 2022
$9.1MBiological annotation of TCGA dataU01CA168394 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI MILLS, GORDON B. · 2012 to 2016
$4.7MTCPA: an Integrated Bioinformatics Resource for Functional Cancer Proteomic DataU24CA209851 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI LIANG, HAN, MILLS, GORDON B. · 2016 to 2020
$4.0MIntegrative bioinformatics and functional characterization of oncogenic driver aberrations in cancerU01CA217842 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DENEEN, BENJAMIN, MILLS, GORDON B. · 2017 to 2021
$3.6MNCI NIH HHS P01 CA120964NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS P50 CA098258NCI NIH HHS P50 CA101942NCI NIH HHS R01 CA175486NCI NIH HHS R21 CA191687NCI NIH HHS U01 CA168394NCI NIH HHS U01 CA217842NCI NIH HHS U24 CA143883NCI NIH HHS U24 CA209851NCI NIH HHS U24 CA210949NCI NIH HHS U24 CA210950
Abstract
Molecular alterations involving the PI3K/AKT/mTOR pathway (including mutation, copy number, protein, or RNA) were examined across 11,219 human cancers representing 32 major types. Within specific mutated genes, frequency, mutation hotspot residues, in silico predictions, and functional assays were all informative in distinguishing the subset of genetic variants more likely to have functional relevance. Multiple oncogenic pathways including PI3K/AKT/mTOR converged on similar sets of downstream transcriptional targets. In addition to mutation, structural variations and partial copy losses involving PTEN and STK11 showed evidence for having functional relevance. A substantial fraction of cancers showed high mTOR pathway activity without an associated canonical genetic or genomic alteration, including cancers harboring IDH1 or VHL mutations, suggesting multiple mechanisms for pathway activation.
Indexed as
ProteogenomicsDatabases, GeneticGene Expression ProfilingHumansMutationNeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktSignal TransductionSurvival AnalysisTOR Serine-Threonine KinasesMTOR protein, humanPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine Kinasesintegrative genomics analysispan-cancer analysisPI3K/AKT/mTOR pathwayproteomicsreverse-phase protein arraysThe Cancer Genome Atlas
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