Evidence map›Paper›PMID 30391357›Full record

ArticleCancer letters2019

Immuno-oncology agent IPI-549 is a modulator of P-glycoprotein (P-gp, MDR1, ABCB1)-mediated multidrug resistance (MDR) in cancer: In vitro and in vivo.

Albert A De Vera, Pranav Gupta, Zining Lei, Dan Liao, Silpa Narayanan, Qiuxu Teng, Sandra E Reznik, Zhe-Sheng Chen

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

Article in Cancer letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 9% 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

31 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.

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  8. FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024
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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 2 institutions in 1 country.

Albert A De VeraDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Pranav GuptaDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Zining LeiDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Dan LiaoDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Silpa NarayananDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Qiuxu TengDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA.
Sandra E ReznikDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA; Department of Pathology and Obstetrics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA; Department of Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. Electronic address: rezniks@stjohns.edu.
Zhe-Sheng ChenDepartment of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. Electronic address: chenz@stjohns.edu.
St. John's University · USAlbert Einstein College of Medicine · US

Funding

Nanowaveguide Illuminated Fluorescence Spectroscopy for Studying Membrane Protein DynamicsR15GM116043 · NIGMS · ST. JOHN'S UNIVERSITY · PI CHEN, ZHE-SHENG · 2015 to 2015
$396k
Targeting MRP7 to Overcome Drug Resistance for Ovarian Cancer Therapy by TaxanesR15CA143701 · NCI · ST. JOHN'S UNIVERSITY · PI CHEN, ZHE-SHENG · 2010 to 2010
$245k
NCI NIH HHS R15 CA143701NIGMS NIH HHS R15 GM116043
6 · The paper itself

Abstract

Phosphoinositide 3-kinase gamma isoform (PI3Kγ) plays a critical role in myeloid-derived cells of the immunosuppressive tumor microenvironment. IPI-549, a recently discovered small molecule selective PI3Kγ inhibitor, is currently under immuno-oncology clinical trials in combination with nivolumab, an anti-PD-1 monoclonal antibody immune checkpoint blocker. The purpose of this study is to investigate whether IPI-549 could reverse P-glycoprotein (P-gp)-mediated MDR when combined with chemotherapeutic substrates of P-gp. Cytotoxicity assays showed that IPI-549 reverses P-gp-mediated MDR in SW620/Ad300 and LLC-PK-MDR1 cells. IPI-549 increases the amount of intracellular paclitaxel and inhibits the efflux of paclitaxel out of SW620/Ad300 cells. ABCB1-ATPase assay showed that IPI-549 stimulates the activity of ABCB1-ATPase. IPI-549 does not alter the expression and does not affect the subcellular localization of P-gp in SW620/Ad300 cells. The combination of IPI-549 with paclitaxel showed that IPI-549 potentiates the anti-tumor effects of paclitaxel in P-gp-overexpressing MDR SW620/Ad300 xenograft tumors. With clinical trials beginning to add newly approved immune checkpoint-based immunotherapy into standard-of-care immunogenic chemotherapy to improve patient outcomes, our findings support the rationale of adding IPI-549 to both the chemotherapeutic and immunotherapeutic aspects of cancer combination treatment strategies.

Indexed as

Phosphoinositide-3 Kinase InhibitorsAnimalsAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Binding SitesClass Ib Phosphatidylinositol 3-KinaseColonic NeoplasmsDrug Resistance, MultipleDrug Resistance, NeoplasmHumansLLC-PK1 CellsMaleMice, NudeMolecular Docking SimulationNeoplasm ProteinsABCB1 protein, humanABCG2 protein, humanAntineoplastic AgentsATP Binding Cassette Transporter, Subfamily BATP Binding Cassette Transporter, Subfamily G, Member 2Class Ib Phosphatidylinositol 3-KinaseNeoplasm ProteinsPaclitaxelPhosphoinositide-3 Kinase InhibitorsPIK3CG protein, humanProtein Kinase InhibitorsABCB1 transporterCombination chemotherapyImmune checkpointIPI-549Multidrug resistanceP-glycoprotein

Identifiers

PMID30391357
PMCPMC6348084
OpenAlexW2898716626

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.