Evidence map›Paper›PMID 31235758›Full record

ArticleScientific reports2019

HER3 targeting potentiates growth suppressive effects of the PI3K inhibitor BYL719 in pre-clinical models of head and neck squamous cell carcinoma.

Kara S Meister, Neal R Godse, Nayel I Khan, Matthew L Hedberg, Carolyn Kemp, Sucheta Kulkarni, Diego Alvarado, Theresa LaVallee, Seungwon Kim, Jennifer R Grandis and 1 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022
    Review
  6. Article
  7. Article
  8. Article
  9. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Kara S MeisterDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.ORCID http://orcid.org/0000-0002-4983-3068
Neal R GodseDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Nayel I KhanDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Matthew L HedbergDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.ORCID http://orcid.org/0000-0002-2810-9724
Carolyn KempDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Sucheta KulkarniDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Diego AlvaradoKolltan Pharmaceuticals, New Haven, CT, USA.
Theresa LaValleeKolltan Pharmaceuticals, New Haven, CT, USA.
Seungwon KimDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA.
Jennifer R GrandisDepartment of Otolaryngology-Head & Neck Surgery, University of California-San Francisco, San Francisco, CA, USA.
Umamaheswar DuvvuriDepartment of Otolaryngology-Head & Neck Surgery, University of Pittsburgh Medical Center, Eye and Ear Institute, Suite 500, 200 Lothrop St., Pittsburgh, PA, 15213, USA. duvvuriu@upmc.edu.
Eye and Ear Foundation · USJazz Pharmaceuticals (United States) · USUniversity of California, San Francisco · US

Funding

UNIVERSITY OF PITTSBURGH CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTE: BPCAUL1RR024153 · NCRR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2006 to 2011
$73.9M
University of Pittsburgh Clinical and Translational Science InstituteUL1TR000005 · NCATS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E · 2012 to 2015
$50.8M
Integrating genomics and the protein interactome for HPV+ head and neck cancer therapyR35CA231998 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2018 to 2024
$6.2M
GRPR Signaling in SCCHN: Integration with EGFRR01CA098372 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI GRANDIS, JENNIFER RUBIN · 2004 to 2017
$3.8M
PROCESSING OF TASTE MIXTURES BY BRAINSTEM NEURONSR01DC000066 · NIDCD · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI WATERS, ROBERT S · 1990 to 2007
$2.4M
Inhibition of lysosomal flux in carcinogen-induced head and neck cancerR01DE028343 · NIDCR · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUVVURI, UMAMAHESWAR · 2019 to 2023
$1.9M
Research Training in OtolaryngologyT32DC000066 · NIDCD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI JOHNSON, JONAS T. · 2003 to 2017
$1.8M
Novel targets to treat head and neck cancer in VeteransI01BX003456 · VA · VETERANS HEALTH ADMINISTRATION · PI DUVVURI, UMAMAHESWAR · 2017 to 2021
–
BLRD VA I01 BX003456NCATS NIH HHS UL1 TR000005NCRR NIH HHS UL1 RR024153NIDCD NIH HHS R01 DC000066NIDCD NIH HHS T32 DC000066NIDCR NIH HHS R01 DE028343
6 · The paper itself

Abstract

BYL719 is a PI3K inhibitor that has demonstrated efficacy in the treatment of head and neck squamous cell carcinoma. BYL719 exerts its therapeutic effect by suppressing AKT and other proliferative signaling mechanisms. Despite PI3K inhibition and AKT suppression, residual activity of protein S6, a core marker of proliferative activation, has been observed. HER3, either via dimerization or activation by its ligand neurgeulin (NRG), is known to activate PI3K. Thus, we hypothesized that co-targeting HER3 and PI3K would lead to greater suppression of the PI3K-AKT signaling pathway and greater tumor suppression than with BYL719 alone. We investigated biochemical expression and activation of the HER3-PI3K-AKT-S6 pathway in HNSCC cell lines and patient-derived xenografts (PDXs). Antitumor effects of HER3 and PI3K inhibitors alone and in combination were evaluated in cell culture and murine models. Treatment of HNSCC cell lines with BYL719 significantly reduced AKT activation and suppressed tumor growth. However, S6 was persistently activated despite suppression of AKT. Combination treatment with KTN3379, a monoclonal antibody targeted against HER3, and BYL719 led to enhanced suppression of in vitro and in vivo cancer growth and durable suppression of AKT and S6. Therefore, inhibition of HER3 with KTN3379 enhanced the effects of PI3K inhibition in pre-clinical HNSCC models. These data support co-targeting HER3 and PI3K for the treatment of HSNCC.

Indexed as

Molecular Targeted TherapyAnimalsCell Line, TumorCell ProliferationDrug SynergismHumansMicePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktReceptor, ErbB-3Signal TransductionSquamous Cell Carcinoma of Head and NeckThiazolesUp-RegulationXenograft Model Antitumor AssaysAlpelisibERBB3 protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktReceptor, ErbB-3Thiazoles

Identifiers

PMID31235758
PMCPMC6591241
OpenAlexW2953427566

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.