Evidence map›Paper›PMID 32087759›Full record

ArticleJournal of hematology & oncology2020

Combination of PI3K and MEK inhibitors yields durable remission in PDX models of PIK3CA-mutated metaplastic breast cancers.

F Coussy, R El Botty, M Lavigne, C Gu, L Fuhrmann, A Briaux, L de Koning, A Dahmani, E Montaudon, L Morisset and 10 more

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

Article in Journal of hematology & oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
2.6field-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

41 citing papers in PubMed, 53 citations in OpenAlex.

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  14. Patient-Derived Xenografts of Breast Cancer.Advances in experimental medicine and biology · 2025
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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

20 authors at 6 institutions in 2 countries.

F CoussyUnit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France. florence.coussy@curie.fr.ORCID 0000-0002-6443-8883
R El BottyLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
M LavigneDepartment of Biopathology, Institut Curie, Paris, France.
C GuDepartment of Biopathology, Institut Curie, Paris, France.
L FuhrmannDepartment of Biopathology, Institut Curie, Paris, France.
A BriauxUnit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.
L de KoningTranslational Research Department, RPPA Platform, Institut Curie Research Center, Paris, France.
A DahmaniLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
E MontaudonLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
L MorissetLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
L HuguetLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
L SourdLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
P PainsecLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
S Chateau-JoubertBioPôle Alfort, National Veterinary School of Alfort, Maison Alfort, France.
T LarcherINRA, APEX-PAnTher, Oniris, Nantes, France.
S VacherUnit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.
S MelaabiUnit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.
A Vincent SalomonDepartment of Biopathology, Institut Curie, Paris, France.
E MarangoniLaboratory of Preclinical Investigation, Department of Translational Research, Institut Curie Research Center, Paris, France.
I BiecheUnit of Pharmacogenomics, Department of Genetics, Institut Curie, Paris, France.
Translational Research in Oncology · FRInstitut Curie · FRIstituto Nazionale Biostrutture e Biosistemi · ITDélégation Paris 5 · FRÉcole Nationale Vétérinaire d'Alfort · FROniris · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMetaplastic breast cancer (MBC) is a rare form of breast cancer characterized by an aggressive clinical presentation, with a poor response to standard chemotherapy. MBCs are typically triple-negative breast cancers (TNBCs), frequently with alterations to genes of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. The objective of this study was to determine the response to PI3K and MAPK pathway inhibitors in patient-derived xenografts (PDXs) of MBCs with targetable alterations.

methodsWe compared survival between triple-negative MBCs and other histological subtypes, in a clinical cohort of 323 TNBC patients. PDX models were established from primary breast tumors classified as MBC. PI3K-AKT-mTOR and RTK-MAPK pathway alterations were detected by targeted next-generation sequencing (NGS) and analyses of copy number alterations. Activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways was analyzed with reverse-phase protein arrays (RPPA). PDXs carrying an activating mutation of PIK3CA and genomic changes to the RTK-MAPK signaling pathways were treated with a combination consisting of a PI3K inhibitor and a MEK inhibitor.

resultsIn our clinical cohort, the patients with MBC had a worse prognosis than those with other histological subtypes. We established nine metaplastic TNBC PDXs. Three had a pathogenic mutation of PIK3CA and additional alterations to genes associated with RTK-MAPK signaling. The MBC PDXs expressed typical EMT and stem cell genes and were of the mesenchymal or mesenchymal stem-like TNBC subtypes. On histological analysis, MBC PDXs presented squamous or chondroid differentiation. RPPA analysis showed activation of the PI3K-AKT-mTOR and RTK-MAPK signaling pathways. In vivo, the combination of PI3K and MAPK inhibitors displayed marked antitumor activity in PDXs carrying genomic alterations of PIK3CA, AKT1, BRAF, and FGFR4.

conclusionThe treatment of metaplastic breast cancer PDXs by activation of the PI3K-AKT-mTOR and RTK-MAPK pathways at the genomic and protein levels with a combination of PI3K and MEK inhibitors resulted in tumor regression in mutated models and may therefore be of interest for therapeutic purposes.

Indexed as

AdultAgedAged, 80 and overAnimalsAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesHumansMice, NudeMiddle AgedMitogen-Activated Protein Kinase KinasesMutationPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProtein Kinase InhibitorsProto-Oncogene Proteins c-aktSignal TransductionAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesMitogen-Activated Protein Kinase KinasesMTOR protein, humanPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPIK3CA protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesCombination of targeted therapiesMEK inhibitorMetaplastic breast cancerPI3K inhibitor

Identifiers

PMID32087759
PMCPMC7036180
OpenAlexW3012522776

What OpenQuestion holds

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LicenceCC BY
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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.