Evidence map›Paper›PMID 28848242›Full record

ArticleNature communications2017

Systems analysis of apoptotic priming in ovarian cancer identifies vulnerabilities and predictors of drug response.

Ioannis K Zervantonakis, Claudia Iavarone, Hsing-Yu Chen, Laura M Selfors, Sangeetha Palakurthi, Joyce F Liu, Ronny Drapkin, Ursula Matulonis, Joel D Leverson, Deepak Sampath and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

37 citing papers in PubMed, 74 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

12 authors at 6 institutions in 2 countries.

Ioannis K ZervantonakisDepartment of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA, 02115, USA.ORCID http://orcid.org/0000-0003-2386-9553
Claudia IavaroneDepartment of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA, 02115, USA.
Hsing-Yu ChenDepartment of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA, 02115, USA.
Laura M SelforsDepartment of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA, 02115, USA.
Sangeetha PalakurthiBelfer Center for Applied Cancer Research, Dana Farber Cancer Institute, Boston, MA, 02115, USA.
Joyce F LiuDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 02115, USA.
Ronny DrapkinPenn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, 19104, USA.ORCID http://orcid.org/0000-0002-6912-6977
Ursula MatulonisDepartment of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, 02115, USA.
Joel D LeversonOncology Development, AbbVie, Inc, North Chicago, IL, 60064, USA.
Deepak SampathTranslational Oncology, Genentech, South San Francisco, CA, 94080, USA.
Gordon B MillsDepartment of Systems Biology, MD Anderson Cancer Center, Houston, TX, 77030, USA.
Joan S BruggeDepartment of Cell Biology, Ludwig Center at Harvard, Harvard Medical School, Boston, MA, 02115, USA. joan_brugge@hms.harvard.edu.
Harvard University · USDana-Farber Cancer Institute · USAbbVie (United States) · USThe University of Texas MD Anderson Cancer Center · USTranslational Research in Oncology · FRUniversity of Pennsylvania · US

Funding

U.T. M. D. Anderson Cancer Center SPORE in Ovarian CancerP50CA217685 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SOOD, ANIL K · 2017 to 2021
$7.9M
NCI NIH HHS P50 CA217685
6 · The paper itself

Abstract

The lack of effective chemotherapies for high-grade serous ovarian cancers (HGS-OvCa) has motivated a search for alternative treatment strategies. Here, we present an unbiased systems-approach to interrogate a panel of 14 well-annotated HGS-OvCa patient-derived xenografts for sensitivity to PI3K and PI3K/mTOR inhibitors and uncover cell death vulnerabilities. Proteomic analysis reveals that PI3K/mTOR inhibition in HGS-OvCa patient-derived xenografts induces both pro-apoptotic and anti-apoptotic signaling responses that limit cell killing, but also primes cells for inhibitors of anti-apoptotic proteins. In-depth quantitative analysis of BCL-2 family proteins and other apoptotic regulators, together with computational modeling and selective anti-apoptotic protein inhibitors, uncovers new mechanistic details about apoptotic regulators that are predictive of drug sensitivity (BIM, caspase-3, BCL-X

Indexed as

ApoptosisAntineoplastic AgentsFemaleHumansMyeloid Cell Leukemia Sequence 1 ProteinOvarian NeoplasmsPhosphatidylinositol 3-KinasesSystems BiologyTOR Serine-Threonine KinasesX-Linked Inhibitor of Apoptosis ProteinAntineoplastic AgentsMCL1 protein, humanMyeloid Cell Leukemia Sequence 1 ProteinPhosphatidylinositol 3-KinasesTOR Serine-Threonine KinasesXIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID28848242
PMCPMC5573720
OpenAlexW2745902885

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.