Evidence map›Paper›PMID 33305187›Full record

ArticleiScience2020

SHP2 Inhibition Influences Therapeutic Response to Tepotinib in Tumors with MET Alterations.

Linda Pudelko, Frank Jaehrling, Christof Reusch, Sanziago Vitri, Christopher Stroh, Nina Linde, Michael P Sanderson, Doreen Musch, Catherine Jorand Lebrun, Marina Keil and 5 more

Open access · goldAbstract read
In one paragraph

Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-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

11 citing papers in PubMed, 21 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

15 authors at 3 institutions in 3 countries.

Linda PudelkoTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Frank JaehrlingTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Christof ReuschTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Sanziago VitriRosell Oncology Institute (IOR), Dexeus University Hospital, QuironSalud Group, 08028 Barcelona, Spain.
Christopher StrohTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Nina LindeTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Michael P SandersonTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Doreen MuschTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Catherine Jorand LebrunMedicinal Chemistry, EMD Serono, Billerica, MA 01821, USA.
Marina KeilTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Christina EsdarTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Andree BlaukatTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Rafael RosellRosell Oncology Institute (IOR), Dexeus University Hospital, QuironSalud Group, 08028 Barcelona, Spain.
Karl Maria SchumacherGlobal Clinical Development, Merck KGaA, Darmstadt 64293, Germany.
Niki KarachaliouTranslational Innovation Platform Oncology, Merck KGaA, Darmstadt 64293, Germany.
Merck (Germany) · DEInstituto Oncológico Dr. Rosell · ESOno Pharmaceutical (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Tepotinib is an oral MET inhibitor approved for metastatic non-small cell lung cancer (NSCLC) harboring MET exon 14 (METex14) skipping mutations. Examining treatment-naive or tepotinib-resistant cells with MET amplification or METex14 skipping mutations identifies other receptor tyrosine kinases (RTKs) that co-exist in cells prior to tepotinib exposure and become more prominent upon tepotinib resistance. In a small cohort of patients with lung cancer with MET genetic alterations treated with tepotinib, gene copy number gains of other RTKs were found at baseline and affected treatment outcome. An Src homology 2 domain-containing phosphatase 2 (SHP2) inhibitor delayed the emergence of tepotinib resistance and synergized with tepotinib in treatment-naive and tepotinib-resistant cells as well as in xenograft models. Alternative signaling pathways potentially diminish the effect of tepotinib monotherapy, and the combination of tepotinib with an SHP2 inhibitor enables the control of tumor growth in cells with MET genetic alterations.

Indexed as

CancerTreatment

Identifiers

PMID33305187
PMCPMC7718487
OpenAlexW3110207998

What OpenQuestion 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 OpenQuestion graph.