Evidence map›Paper›PMID 29754184›Full record

ArticleTargeted oncology2018

Discovery of a Potent and Mutant-Selective EGFR Inhibitor that Overcomes T790M-Mediated Resistance in Lung Cancer.

Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Young Hoon Sung, Woo Sung Kim, Sung-Eun Kim, Hyung Chul Ryu, Jae Sun Kim and 4 more

Abstract read
PubMed Publisher
In one paragraph

Article in Targeted oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 38% 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

1 citing paper in PubMed, 4 citations in OpenAlex.

  1. Article
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 5 institutions in 2 countries.

Dong Ha KimDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Yun Jung ChoiDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Seon Ye KimDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Jung-Eun LeeDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Ki Jung SungDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Young Hoon SungAsan Institute for Life Sciences, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Woo Sung KimDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Sung-Eun KimOncobix, Yongin, 16950, South Korea.
Hyung Chul RyuJ2H Biotech, Ansan, 16648, South Korea.
Jae Sun KimJ2H Biotech, Ansan, 16648, South Korea.
Lu GuangyingEast China University of Science and Technology, College of Pharmacy, Shanghai, 200237, China.
Chang-Min ChoiDepartment of Pulmonology and Critical Care Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea.
Jin Kyung RhoDepartment of Convergence Medicine, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea. jkrho@amc.seoul.kr.
Jae Cheol LeeDepartment of Oncology, Asan Medical Center, University of Ulsan, College of Medicine, Seoul, 05505, South Korea. jclee@amc.seoul.kr.
Ulsan College · KRUniversity of Ulsan · KRSTR Biotech (South Korea) · KRAsan Medical Center · KREast China University of Science and Technology · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDespite remarkable activity in epidermal growth factor receptor (EGFR)-mutant lung cancer patients, the clinical efficacy of EGFR tyrosine kinase inhibitors (TKIs) is limited by the emergence of acquired resistance, which is mostly caused by a secondary T790M mutation. Fortunately, newly developed, mutant-selective EGFR-TKIs against T790M have been proven as an effective therapeutic approach although only osimertinib has received the FDA approval until now.

objectiveTo determine the in vitro and in vivo efficacy of a new EGFR TKI, OBX1-012 in cells with mutant EGFR.

methodsEffects of OBX1-012 on cellular viability and EGFR-related signaling were determined in EGFR-mutant non-small cell lung cancer (NSCLC) cells, including cells harboring T790M mutations. In addition, in vivo efficacy of OBX1-012 was evaluated in xenograft models.

resultsWe report the discovery and preclinical assessment of another novel, mutant-selective EGFR-TKI, OBX1-012. Compared with other mutant-selective EGFR-TKIs such as olumitinib and osimertinib, it showed similar potency and selectivity for mutant EGFR. OBX1-012 treatment was highly effective against human EGFR-mutant lung cancer models with or without EGFR T790M, not only in vitro but also in vivo. However, OBX1-012 like other EGFR-TKIs failed to exhibit efficacy for the exon 20 insertion mutation or C797S mutation, which was generated by site-directed mutagenesis and stable transfection of Ba/F3 cells.

conclusionsThese results identify OBX1-012 as a highly effective, mutant-selective EGFR-TKI for the treatment of T790M-mediated resistance in NSCLC.

Indexed as

Cell Line, TumorDrug Resistance, NeoplasmHumansLung NeoplasmsProtein Kinase InhibitorsProtein Kinase Inhibitors

Identifiers

PMID29754184
OpenAlexW3005078328

What OpenQuestion holds

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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.