ArticleScience translational medicine2017
The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation.
Erratum issuedAbstract read
In one paragraph
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 73 papers.
0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
6.4field-weighted citation impact, top 2% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
73 citing papers in PubMed, 110 citations in OpenAlex.
- Article
- Deciphering and Targeting the Schwannoma-Neuron-Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Breast cancer brain metastasis: from molecular insights to therapeutic innovation.Frontiers in immunology · 2026Review
- Establishment and validation of an orthotopic brain metastasis tumor model in C57BL/6 mice.PeerJ · 2026Article
- Oligodendrocyte-secreted ERBB3 Mediates the Competitive Uptake of Copper Ions by Tumor Cells to Promote Brain Metastasis in Lung Cancer.International journal of biological sciences · 2026Article
- Incidence and prognosis of brain metastases in esophageal carcinoma: a systematic review and meta-analysis.Journal of thoracic disease · 2025Article
- Systemic HER3 ligand-mimicking nanobioparticles enter the brain and reduce intracranial tumour growth.Nature nanotechnology · 2025Article
- Emerging importance of HER3 in tumorigenesis and cancer therapy.Nature reviews. Clinical oncology · 2025Review
- Molecular evolution of central nervous system metastasis and therapeutic implications.Trends in molecular medicine · 2025Review
- The Biological Roles and Clinical Applications of the PI3K/AKT Pathway in Targeted Therapy Resistance in HER2-Positive Breast Cancer: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Antibody-Drug Conjugates for the Treatment of Non-Small Cell Lung Cancer with Central Nervous System Metastases.Current oncology (Toronto, Ont.) · 2024Review
- DUSP6 inhibition overcomes neuregulin/HER3-driven therapy tolerance in HER2+ breast cancer.EMBO molecular medicine · 2024Article
- Characterizing heterogeneous single-cell dose responses computationally and experimentally using threshold inhibition surfaces and dose-titration assays.NPJ systems biology and applications · 2024Article
- Targeted Hyperbranched Nanoparticles for Delivery of Doxorubicin in Breast Cancer Brain Metastasis.Molecular pharmaceutics · 2023Article
- Ligand-based active targeting strategies for cancer theranostics.Naunyn-Schmiedeberg's archives of pharmacology · 2023Review
- Intravital measurements of solid stresses in tumours reveal length-scale and microenvironmentally dependent force transmission.Nature biomedical engineering · 2023Article
- Limiting mitochondrial plasticity by targeting DRP1 induces metabolic reprogramming and reduces breast cancer brain metastases.Nature cancer · 2023Article
- Review
- Functional biomaterials for biomimetic 3D in vitro tumor microenvironment modeling.In vitro models · 2023Review
- A review on genetic alterations in CNS metastases related to breast cancer treatment. Is there a role for liquid biopsies in CSF?Journal of neuro-oncology · 2023Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
33 authors at 7 institutions in 2 countries.
David P KodackEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0001-8565-334X
Vasileios AskoxylakisEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0002-2594-3019
Gino B FerraroEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Qing ShengOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID 0000-0002-5435-8177
Mark BadeauxEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Shom GoelEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Xiaolong QiEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Ram ShankaraiahEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0001-9824-0560
Z Alexander CaoOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Rakesh R RamjiawanEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0001-5640-4256
Divya BezwadaEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Bhushankumar PatelEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Yongchul SongDepartment of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.ORCID 0000-0001-5681-6429
Carlotta CostaDepartment of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.
Kamila NaxerovaEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0001-7744-5110
Christina S F WongEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0002-1650-5383
Jonas KloepperEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0003-3507-8599
Rita DasOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID 0000-0001-9778-9447
Angela TamOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID 0000-0003-0244-0109
Jantima TanboonDepartment of Pathology, MGH and HMS, Boston, MA 02114, USA.ORCID 0000-0002-4110-9198
Dan G DudaEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0001-7065-8797
C Ryan MillerDepartment of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-0096-8762
Marni B SiegelDepartment of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.ORCID 0000-0002-0807-4368
Carey K AndersDivision of Hematology Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
Melinda SandersDepartment of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.ORCID 0000-0001-7227-1764
Monica V EstradaBreast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.ORCID 0000-0001-9846-8223
Robert SchlegelOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Carlos L ArteagaDepartments of Medicine and Cancer Biology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
Elena BrachtelDepartment of Pathology, MGH and HMS, Boston, MA 02114, USA.
Alan HuangOncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.ORCID 0000-0001-5501-0212
Dai FukumuraEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.ORCID 0000-0002-9505-4444
Jeffrey A EngelmanDepartment of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA. jain@steele.mgh.harvard.edu jeffrey.engelman@novartis.com.
Rakesh K JainEdwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA. jain@steele.mgh.harvard.edu jeffrey.engelman@novartis.com.ORCID 0000-0001-7571-3548
Massachusetts General Hospital · USNovartis (Switzerland) · CHCenter for Cancer Research · USUniversity of North Carolina at Chapel Hill · USMGH Institute of Health Professions · USVanderbilt University · USBreast Cancer Research Foundation · US
Funding
TISSUE CoreP50CA098131 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI PARK, BEN HO, PIETENPOL, JENNIFER A · 2003 to 2024
$48.7MVascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SEED, BRIAN · 2000 to 2016
$35.0MTargeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Benjamin Harris Kann · 2013 to 2026
$33.5MTRD3: Percutaneous and Interstitial ImagingP41EB015903 · NIBIB · MASSACHUSETTS GENERAL HOSPITAL · PI Brett E Bouma · 2012 to 2026
$22.4MProbing Tumor Microenvironment Using NanotechnologyR01CA126642 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2008 to 2012
$8.3MDissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7MThe Activation of ERBB3 Signaling as a Resistance Mechanism to Targeted TherapiesR01CA137008 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Aaron N Hata, ZOFIA PIOTROWSKA · 2009 to 2026
$5.7MNO in Tumor Angiogenesis,Microcirculation &Rad.TherapyR01CA096915 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI · 2002 to 2012
$3.0MTraining Program in Pathophysiology of Solid TumorsT32CA073479 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 1998 to 2012
$3.0MReengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2MEstablishing Genetic Drivers of Breast Cancer MetastasesF30CA200345 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SIEGEL, MARNI B · 2015 to 2018
$151kNCI NIH HHS F30 CA200345NCI NIH HHS P01 CA080124NCI NIH HHS P50 CA098131NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA096915NCI NIH HHS R01 CA126642NCI NIH HHS R01 CA137008NCI NIH HHS R01 CA208205NCI NIH HHS R35 CA197743NCI NIH HHS T32 CA073479NIBIB NIH HHS P41 EB015903
Abstract
Although targeted therapies are often effective systemically, they fail to adequately control brain metastases. In preclinical models of breast cancer that faithfully recapitulate the disparate clinical responses in these microenvironments, we observed that brain metastases evade phosphatidylinositide 3-kinase (PI3K) inhibition despite drug accumulation in the brain lesions. In comparison to extracranial disease, we observed increased HER3 expression and phosphorylation in brain lesions. HER3 blockade overcame the resistance of
Indexed as
AnimalsAntineoplastic AgentsBrain NeoplasmsBreast NeoplasmsFemaleMicePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsReceptor, ErbB-3Antineoplastic AgentsPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsReceptor, ErbB-3
Identifiers
What OpenQuestion holds
Textmetadata
LicenceTDM
Read underepoch 390
Registered trials
None linked
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.