Evidence map›Paper›PMID 30909453›Full record

ArticleCancers2019

Overactive IGF1/Insulin Receptors and NRASQ61R Mutation Drive Mechanisms of Resistance to Pazopanib and Define Rational Combination Strategies to Treat Synovial Sarcoma.

Cinzia Lanzi, Laura Dal Bo, Enrica Favini, Monica Tortoreto, Giovanni Luca Beretta, Noemi Arrighetti, Nadia Zaffaroni, Giuliana Cassinelli

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

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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

8 authors at 1 institution in 1 country.

Cinzia LanziDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. cinzia.lanzi@istitutotumori.mi.it.ORCID 0000-0002-4480-9413
Laura Dal BoDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. laura.dalbo@istitutotumori.mi.it.
Enrica FaviniDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. enrica.favini@istitutotumori.mi.it.
Monica TortoretoDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. monica.tortoreto@istitutotumori.mi.it.
Giovanni Luca BerettaDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. giovanni.beretta@istitutotumori.mi.it.ORCID 0000-0002-5961-4109
Noemi ArrighettiDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. noemi.arrighetti@istitutotumori.mi.it.
Nadia ZaffaroniDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. nadia.zaffaroni@istitutotumori.mi.it.
Giuliana CassinelliDepartment of Applied Research and Technological Development, Molecular Pharmacology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Amadeo 42, 20133 Milan, Italy. giuliana.cassinelli@istitutotumori.mi.it.
Fondazione IRCCS Istituto Nazionale dei Tumori · IT

Funding

Associazione Bianca Garavaglia A/18/01B
6 · The paper itself

Abstract

Pazopanib is approved for treatment of advanced soft tissue sarcomas, but primary and secondary drug resistance limits its clinical utility. We investigated the molecular mechanisms mediating pazopanib resistance in human synovial sarcoma (SS) models. We found reduced cell sensitivity to pazopanib associated with inefficient inhibition of the two critical signaling nodes, AKT and ERKs, despite strong inhibition of the main drug target, PDGFRα. In the CME-1 cell line, overactivation of IGF1 and Insulin receptors (IGF1R/InsR) sustained AKT activation and pazopanib resistance, which was overcome by a combination treatment with the double IGF1R/InsR inhibitor BMS754807. In the highly pazopanib resistant MoJo cell line, NRASQ61R mutation sustained constitutive ERK activation. Transfection of the NRAS mutant in the pazopanib sensitive SYO-1 cell line increased the drug IC

Indexed as

BMS754807drug resistanceNRAS mutationorthotopic sarcoma xenograftpazopanibsynovial sarcomatrametinib

Identifiers

PMID30909453
PMCPMC6468361
OpenAlexW2923678061

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.