Evidence map›Paper›PMID 32911681›Full record

ArticleCancers2020

Multi-Omics Investigation of Innate Navitoclax Resistance in Triple-Negative Breast Cancer Cells.

Michal Marczyk, Gauri A Patwardhan, Jun Zhao, Rihao Qu, Xiaotong Li, Vikram B Wali, Abhishek K Gupta, Manoj M Pillai, Yuval Kluger, Qin Yan and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 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, 19 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

13 authors at 3 institutions in 2 countries.

Michal MarczykYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.ORCID 0000-0003-2508-5736
Gauri A PatwardhanYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Jun ZhaoComputational Biology & Bioinformatics Program, Yale University, New Haven, CT 06511, USA.
Rihao QuComputational Biology & Bioinformatics Program, Yale University, New Haven, CT 06511, USA.
Xiaotong LiYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.ORCID 0000-0003-1644-6835
Vikram B WaliYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Abhishek K GuptaYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Manoj M PillaiYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Yuval KlugerComputational Biology & Bioinformatics Program, Yale University, New Haven, CT 06511, USA.
Qin YanDepartment of Pathology, Yale School of Medicine, New Haven, CT 06511, USA.ORCID 0000-0003-4077-453X
Christos HatzisYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Lajos PusztaiYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.
Vignesh GunasekharanYale Cancer Center, Yale School of Medicine, New Haven, CT 06511, USA.ORCID 0000-0002-2471-8485
Yale Cancer Center · USYale University · USSilesian University of Technology · PL

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Deregulation of SF3B1 function by recurrent HEAT domain mutationsR01HL133406 · NHLBI · YALE UNIVERSITY · PI NEUGEBAUER, KARLA M, PILLAI, MANOJ M. · 2017 to 2020
$1.7M
EFFICIENT METHODS FOR CALIBRATION, CLUSTERING, VISUALIZATION AND IMPUTATION OF LARGE scRNA-seq DATAR01GM131642 · NIGMS · YALE UNIVERSITY · PI KLUGER, YUVAL · 2019 to 2022
$1.6M
Breast Cancer Research Foundation LPNCATS NIH HHS UL1 TR001863NIGMS NIH HHS R01 GM131642NIH HHS R01 HL133406Susan G. Komen SAC160076
6 · The paper itself

Abstract

Cancer cells employ various defense mechanisms against drug-induced cell death. Investigating multi-omics landscapes of cancer cells before and after treatment can reveal resistance mechanisms and inform new therapeutic strategies. We assessed the effects of navitoclax, a BCL2 family inhibitor, on the transcriptome, methylome, chromatin structure, and copy number variations of MDA-MB-231 triple-negative breast cancer (TNBC) cells. Cells were sampled before treatment, at 72 h of exposure, and after 10-day drug-free recovery from treatment. We observed transient alterations in the expression of stress response genes that were accompanied by corresponding changes in chromatin accessibility. Most of these changes returned to baseline after the recovery period. We also detected lasting alterations in methylation states and genome structure that suggest permanent changes in cell population composition. Using single-cell analyses, we identified 2350 genes significantly upregulated in navitoclax-resistant cells and derived an 18-gene navitoclax resistance signature. We assessed the navitoclax-response-predictive function of this signature in four additional TNBC cell lines in vitro and in silico in 619 cell lines treated with 251 different drugs. We observed a drug-specific predictive value in both experiments, suggesting that this signature could help guiding clinical biomarker studies involving navitoclax.

Indexed as

cancer therapydrug resistancemulti-omicsnavitoclaxsignaturetriple-negative breast cancer

Identifiers

PMID32911681
PMCPMC7563413
OpenAlexW3084234945

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.