Evidence map›Paper›PMID 30001368›Full record

ArticlePloS one2018

Downregulation of PIK3CA via antibody-esiRNA-complexes suppresses human xenograft tumor growth.

Nicole Bäumer, Jan Rehkämper, Neele Appel, Lisa Terheyden, Wolfgang Hartmann, Eva Wardelmann, Frank Buchholz, Carsten Müller-Tidow, Wolfgang E Berdel, Sebastian Bäumer

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 36% 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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
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  5. 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

10 authors at 3 institutions in 1 country.

Nicole BäumerDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.ORCID 0000-0002-7530-467X
Jan RehkämperGerhard-Domagk Institute for Pathology, University of Muenster, Muenster, Germany.
Neele AppelDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
Lisa TerheydenDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
Wolfgang HartmannGerhard-Domagk Institute for Pathology, University of Muenster, Muenster, Germany.
Eva WardelmannGerhard-Domagk Institute for Pathology, University of Muenster, Muenster, Germany.
Frank BuchholzUniversitäts KrebsCentrum (UCC), Medical Systems Biology, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Carsten Müller-TidowDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
Wolfgang E BerdelDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
Sebastian BäumerDepartment of Medicine A, Hematology/Oncology, University of Muenster, Muenster, Germany.
University of Münster · DEGerman Cancer Research Center · DEHeidelberg University · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Precision cancer therapy requires on the one hand detailed knowledge about a tumor's driver oncogenes and on the other hand an effective targeted therapy that specifically inhibits these oncogenes. While the determination of genomic landscape of a tumor has reached a very precise level, the respective therapy options are scarce. The application of small inhibitory (si) RNAs is a promising field of investigation. Here, we present the effective in vivo-treatment of colorectal cancer (CRC) xenograft tumors with antibody-complexed, endoribonuclease-prepared small inhibitory (esi)RNAs. We chose heterogeneous endoribonuclease-prepared siRNA pools (esiRNAs) against the frequently mutated genes PIK3CA and KRAS and coupled them to the anti-EGFR antibody cetuximab, which was internalized specifically into the tumor cells. esiRNA pools have been shown to exhibit superior specificity in target gene knockdown compared to classic siRNAs. We identified a significant decrease in tumor growth upon this treatment due to decreased tumor cell proliferation. The ex vivo-analysis of the xenograft CRC tumors revealed the expected downregulation of the intended direct targets PIK3CA and KRAS on protein level. Moreover, known downstream targets for EGFR signaling such as p-ERK, p-AKT, and c-MYC were decreased as well. We therefore propose the use of antibody-esiRNA complexes as a novel experimental treatment option against key components of the EGFR signaling cascade.

Indexed as

AnimalsCell Line, TumorCetuximabClass I Phosphatidylinositol 3-KinasesColorectal NeoplasmsCombined Modality TherapyDown-RegulationFemaleHT29 CellsHumansMiceMice, NudeMutationProto-Oncogene Proteins p21(ras)RNA, Small InterferingSignal TransductionCetuximabClass I Phosphatidylinositol 3-KinasesKRAS protein, humanPIK3CA protein, humanProto-Oncogene Proteins p21(ras)RNA, Small Interfering

Identifiers

PMID30001368
PMCPMC6042707
OpenAlexW2853262946

What OpenQuestion holds

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LicenceCC BY
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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.