Evidence map›Paper›PMID 32032474›Full record

ArticleJournal of cellular and molecular medicine2020

Pharmacological screening and transcriptomic functional analyses identify a synergistic interaction between dasatinib and olaparib in triple-negative breast cancer.

Verónica Corrales-Sánchez, María Del Mar Noblejas-López, Cristina Nieto-Jiménez, Javier Pérez-Peña, Juan Carlos Montero, Miguel Burgos, Eva M Galán-Moya, Atanasio Pandiella, Alberto Ocaña

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.7field-weighted citation impact, top 14% 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

12 citing papers in PubMed, 40 citations in OpenAlex.

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  10. MZ1 co-operates with trastuzumab in HER2 positive breast cancer.Journal of experimental & clinical cancer research : CR · 2021
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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

9 authors at 4 institutions in 1 country.

Verónica Corrales-SánchezTranslational Research Unit, Albacete University Hospital, Albacete, Spain.
María Del Mar Noblejas-LópezTranslational Research Unit, Albacete University Hospital, Albacete, Spain.
Cristina Nieto-JiménezTranslational Research Unit, Albacete University Hospital, Albacete, Spain.
Javier Pérez-PeñaTranslational Oncology Laboratory, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, Albacete, Spain.
Juan Carlos MonteroInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Salamanca, Spain.
Miguel BurgosTranslational Research Unit, Albacete University Hospital, Albacete, Spain.
Eva M Galán-MoyaTranslational Oncology Laboratory, Centro Regional de Investigaciones Biomédicas (CRIB), Universidad de Castilla La Mancha, Albacete, Spain.ORCID 0000-0001-5758-7592
Atanasio PandiellaInstituto de Biología Molecular y Celular del Cáncer (IBMCC-CIC), Salamanca, Spain.
Alberto OcañaTranslational Research Unit, Albacete University Hospital, Albacete, Spain.ORCID 0000-0002-1067-9630
Hospital General Universitario de Albacete · ESInstituto de Investigación Biomédica de Salamanca · ESUniversity of Castilla-La Mancha · ESHospital Clínico San Carlos · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Identification of druggable vulnerabilities is a main objective in triple-negative breast cancer (TNBC), where no curative therapies exist. Gene set enrichment analyses (GSEA) and a pharmacological evaluation using a library of compounds were used to select potential druggable combinations. MTT and studies with semi-solid media were performed to explore the activity of the combinations. TNBC cell lines (MDAMB-231, BT549, HS-578T and HCC3153) and an additional panel of 16 cell lines were used to assess the activity of the two compounds. Flow cytometry experiments and biochemical studies were also performed to explore the mechanism of action. GSEA were performed using several data sets (GSE21422, GSE26910, GSE3744, GSE65194 and GSE42568), and more than 35 compounds against the identified functions were evaluated to discover druggable opportunities. Analyses done with the Chou and Talalay algorithm confirmed the synergy of dasatinib and olaparib. The combination of both agents significantly induced apoptosis in a caspase-dependent manner and revealed a pleotropic effect on cell cycle: Dasatinib arrested cells in G0/G1 and olaparib in G2/M. Dasatinib inhibited pChk1 and induced DNA damage measured by pH2AX, and olaparib increased pH3. Finally, the effect of the combination was also evaluated in a panel of 18 cell lines representative of the most frequent solid tumours, observing a particularly synergism in ovarian cancer. Breast cancer, triple negative, dasatinib, olaparib, screening.

Indexed as

Cell Line, TumorCell ProliferationDasatinibDrug Evaluation, PreclinicalDrug Resistance, NeoplasmDrug SynergismFemaleHumansPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein Kinase InhibitorsTranscriptomeTriple Negative Breast NeoplasmsDasatinibolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsProtein Kinase Inhibitorsbreast cancerdasatinibolaparibscreeningtriple negative

Identifiers

PMID32032474
PMCPMC7077558
OpenAlexW3004921224

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.