Evidence map›Paper›PMID 35108525›Full record

ArticleCell reports2022

Targetable HER3 functions driving tumorigenic signaling in HER2-amplified cancers.

Marcia R Campbell, Ana Ruiz-Saenz, Elliott Peterson, Christopher Agnew, Pelin Ayaz, Sam Garfinkle, Peter Littlefield, Veronica Steri, Julie Oeffinger, Maryjo Sampang and 4 more

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

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Modulating pseudokinase conformation from the ATP-binding site.Structure (London, England : 1993) · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Dual inhibition of HERs and PD-1 counteract resistance in KRASJournal of experimental & clinical cancer research : CR · 2024
    Article
  8. Review
  9. Review
  10. HER3 in cancer: from the bench to the bedside.Journal of experimental & clinical cancer research : CR · 2022
    Review
  11. Article
  12. Article
  13. Review
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

14 authors at 3 institutions in 2 countries.

Marcia R CampbellDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Ana Ruiz-SaenzDepartments of Cell Biology & Medical Oncology, Erasmus Medical Center, Rotterdam, the Netherlands.
Elliott PetersonDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Christopher AgnewCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Pelin AyazD. E. Shaw Research, New York, NY 10036, USA.
Sam GarfinkleD. E. Shaw Research, New York, NY 10036, USA.
Peter LittlefieldCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
Veronica SteriHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Julie OeffingerDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Maryjo SampangDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
Yibing ShanD. E. Shaw Research, New York, NY 10036, USA.
David E ShawD. E. Shaw Research, New York, NY 10036, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
Natalia JuraCardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143, USA.
Mark M MoasserDepartment of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: mark.moasser@ucsf.edu.
University of California, San Francisco · USD. E. Shaw Research · USErasmus MC · NL

Funding

Understanding resistance to HER family tyrosine kinase inhibitorsR01CA122216 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MOASSER, MARK M · 2007 to 2017
$3.0M
Structural and Functional Studies of HER ReceptorsR35GM139636 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Natalia Jura · 2021 to 2026
$2.5M
Structural and Functional Studies of HER Receptor Tyrosine KinasesR01GM109176 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JURA, NATALIA · 2014 to 2018
$1.8M
NCI NIH HHS R01 CA122216NIGMS NIH HHS R01 GM109176NIGMS NIH HHS R35 GM139636
6 · The paper itself

Abstract

Effective inactivation of the HER2-HER3 tumor driver has remained elusive because of the challenging attributes of the pseudokinase HER3. We report a structure-function study of constitutive HER2-HER3 signaling to identify opportunities for targeting. The allosteric activation of the HER2 kinase domain (KD) by the HER3 KD is required for tumorigenic signaling and can potentially be targeted by allosteric inhibitors. ATP binding within the catalytically inactive HER3 KD provides structural rigidity that is important for signaling, but this is mimicked, not opposed, by small molecule ATP analogs, reported here in a bosutinib-bound crystal structure. Mutational disruption of ATP binding and molecular dynamics simulation of the apo KD of HER3 identify a conformational coupling of the ATP pocket with a hydrophobic AP-2 pocket, analogous to EGFR, that is critical for tumorigenic signaling and feasible for targeting. The value of these potential target sites is confirmed in tumor growth assays using gene replacement techniques.

Indexed as

Aniline CompoundsBreast NeoplasmsCarcinogenesisCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleHumansNitrilesQuinolinesReceptor, ErbB-3Signal TransductionAniline CompoundsbosutinibERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanNitrilesQuinolinesReceptor, ErbB-3allosteric inhibitorAP-2 pocketbosutinibbreast cancerERBB2ERBB3HER2HER3

Identifiers

PMID35108525
PMCPMC8889928
OpenAlexW4210678483

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.