Evidence map›Paper›PMID 26517520›Full record

ArticleOncotarget2015

244-MPT overcomes gefitinib resistance in non-small cell lung cancer cells.

Yi Zhang, Ke Yao, Chengcheng Shi, Yanan Jiang, Kangdong Liu, Song Zhao, Hanyong Chen, Kanamata Reddy, Chengjuan Zhang, Xiaoyu Chang and 4 more

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

Article in Oncotarget, 2015. 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
2.6field-weighted citation impact, top 10% 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, 17 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

14 authors at 6 institutions in 2 countries.

Yi ZhangThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Ke YaoThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Chengcheng ShiThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Yanan JiangPathophysiology Department, Basic Medical College, Zhengzhou University, Henan, China.
Kangdong LiuThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Song ZhaoThe First Affiliated Hospital of Zhengzhou University, Henan, China.
Hanyong ChenThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Kanamata ReddyThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Chengjuan ZhangThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Xiaoyu ChangThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Joohyun RyuThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Ann M BodeThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Ziming DongPathophysiology Department, Basic Medical College, Zhengzhou University, Henan, China.
Zigang DongThe Hormel Institute, University of Minnesota, Austin, MN, USA.
Hormel (United States) · USUniversity of Minnesota · USChina-US (Henan) Hormel Cancer Institute · CNFirst Affiliated Hospital of Zhengzhou University · CNHenan Cancer Hospital · CNZhengzhou University · CN

Funding

Chemoprevention of colon cancer by targeting the Wnt/beta-catenin pathwayR01CA187027 · NCI · UNIVERSITY OF MINNESOTA · PI KANG, NINGLING, ROH, EUNMIRI · 2015 to 2019
$1.7M
Developing new ornithine decarboxylase inhibitors to prevent skin & colon cancerR01CA166011 · NCI · UNIVERSITY OF MINNESOTA · PI DONG, ZIGANG · 2013 to 2017
$1.6M
Anticarcinogenic Mechanisms of Tea ConstituentsR37CA081064 · NCI · UNIVERSITY OF MINNESOTA · PI DONG, ZIGANG · 2008 to 2012
$1.5M
Molecular Mechanisms and Targets of Soy Compounds in the Prevention of Colon CancR21CA172457 · NCI · UNIVERSITY OF MINNESOTA · PI DONG, ZIGANG · 2013 to 2014
$327k
NCI NIH HHS R01 CA166011NCI NIH HHS R01 CA187027NCI NIH HHS R21 CA172457NCI NIH HHS R37 CA081064
6 · The paper itself

Abstract

The epidermal growth factor receptor (EGFR) is known to play a critical role in non-small cell lung cancer(NSCLC). Several EGFR tyrosine kinase inhibitors(TKIs), such as gefitinib, have been used as effective clinical therapies for patients with NSCLC. Unfortunately, acquired resistance to gefitinib commonly occurs after 6-12 months of treatment. The resistance is associated with the appearance of the L858R/T790M double mutation of the EGFR. In our present study, we discovered a compound,referred to as 244-MPT, which could suppress either gefitinib-sensitive or -resistant lung cancer cell growth and colony formation, and also suppressed the kinase activity of both wildtype and double mutant (L858R/T790M) EGFR. The underlying mechanism reveals that 244-MPT could interact with either the wildtype or double-mutant EGFR in an ATP-competitive manner and inhibit activity. Treatment with 244-MPT could substantially reduce the phosphorylation of EGFR and its downstream signaling pathways, including Akt and ERK1/2 in gefitinib-sensitive and -resistant cell lines. It was equally effective in suppressing EGFR phosphorylation and downstream signaling in NL20 cells transfected with wildtype, single-mutant (L858R) or mutant (L858R/T790M) EGFR. 244-MPT could also induce apoptosis in a gefitinib-resistant cell line and strongly suppress gefitinib-resistant NSCLC tumor growth in a xenograft mouse model. In addition, 244-MPT could effectively reduce the size of tumors in a gefitinib-resistant NSCLC patient-derived xenograft (PDX) SCID mouse model. Overall, 244-MPT could overcome gefitinib-resistance by directly targeting the EGFR.

Indexed as

AnimalsAntineoplastic AgentsApoptosisCarcinoma, Non-Small-Cell LungCell Line, TumorCell ProliferationDose-Response Relationship, DrugDrug Resistance, NeoplasmEnzyme ActivationErbB ReceptorsExtracellular Signal-Regulated MAP KinasesGefitinibHEK293 CellsHumansLung NeoplasmsMice, Nude2-(4-(4-methoxyphenoxy)-1H-pyrazol-3-yl)-5-(p-tolylmethoxy)phenolAntineoplastic AgentsEGFR protein, humanErbB ReceptorsExtracellular Signal-Regulated MAP KinasesGefitinibPhenolsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktPyrazolesQuinazolinesepidermal growth factor receptor (EGFR)gefitinib resistancenon-small cell lung cancer (NSCLC)

Identifiers

PMID26517520
PMCPMC4792556
OpenAlexW2190716655

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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.