Evidence map›Paper›PMID 36778419›Full record

ArticlebioRxiv : the preprint server for biology2023

CDK4/6 inhibition enhances SHP2 inhibitor efficacy and is dependent upon restoration of RB function in malignant peripheral nerve sheath tumors.

Jiawan Wang, Ana Calizo, Lindy Zhang, James C Pino, Yang Lyu, Kai Pollard, Xiaochun Zhang, Alex T Larsson, Eric Conniff, Nicolas Llosa and 6 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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

0 citing papers in PubMed, 5 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 6 institutions in 3 countries.

Jiawan WangDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
Ana CalizoDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
Lindy ZhangDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
James C PinoPacific Northwest National Laboratory; Seattle, WA, USA.
Yang LyuDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis; St. Louis, MO, USA.
Kai PollardDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
Xiaochun ZhangDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis; St. Louis, MO, USA.
Alex T LarssonDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota; Minneapolis, MN, USA.
Eric ConniffDepartment of Biomedical Engineering, University of Minnesota; Minneapolis, MN, USA.
Nicolas LlosaDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
David K WoodDepartment of Biomedical Engineering, University of Minnesota; Minneapolis, MN, USA.
David A LargaespadaDepartment of Pediatrics, Masonic Cancer Center, University of Minnesota; Minneapolis, MN, USA.
Susan E MoodyNovartis Institutes for Biomedical Research; Cambridge, MA, USA.
Sara J GoslinePacific Northwest National Laboratory; Seattle, WA, USA.
Angela C HirbeDivision of Oncology, Department of Internal Medicine, Siteman Cancer Center, Washington University in St. Louis; St. Louis, MO, USA.
Christine A PratilasDivision of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Department of Oncology and Pediatrics, Johns Hopkins University School of Medicine; Baltimore, MD, USA.
Johns Hopkins University · USWashington University in St. Louis · USMinneapolis Institute of Arts · USPacific Northwest National Laboratory · USUniversity of Minnesota · USNovartis (Switzerland) · CH

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI ALAN KEITH MEEKER · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

Malignant peripheral nerve sheath tumors (MPNST) are highly aggressive soft tissue sarcomas with limited treatment options, and novel effective therapeutic strategies are desperately needed. We observe anti-proliferative efficacy of genetic depletion or pharmacological inhibition using the clinically available SHP2 inhibitor (SHP2i) TNO155. Our studies into the signaling response to SHP2i reveal that resistance to TNO155 is partially mediated by reduced RB function, and we therefore test the addition of a CDK4/6 inhibitor (CDK4/6i) to enhance RB activity and improve TNO155 efficacy. In combination, TNO155 attenuates the adaptive response to CDK4/6i, potentiates its anti-proliferative effects, and converges on enhancement of RB activity, with greater suppression of cell cycle and inhibitor-of-apoptosis proteins, leading to deeper and more durable anti-tumor activity in

Identifiers

PMID36778419
PMCPMC9915673
OpenAlexW4319231016

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.