Evidence map›Paper›PMID 31517048›Full record

ArticleScience advances2019

Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models.

Mandana T Manzari, Gray R Anderson, Kevin H Lin, Ryan S Soderquist, Merve Çakir, Mitchell Zhang, Chandler E Moore, Rachel N Skelton, Maréva Fèvre, Xinghai Li and 5 more

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

Article in Science advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

6 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
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  4. Review
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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

15 authors at 1 institution in 1 country.

Mandana T ManzariDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-1163-9649
Gray R AndersonDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-2493-2510
Kevin H LinDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Ryan S SoderquistDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Merve ÇakirDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
Mitchell ZhangDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
Chandler E MooreDepartment of Neuroscience, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-0951-6383
Rachel N SkeltonDepartment of Neuroscience, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-6144-2983
Maréva FèvreDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.ORCID 0000-0001-6460-9227
Xinghai LiDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
Joseph J BellucciDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
Suzanne E WardellDepartment of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-5792-1447
Simone A CostaDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.
Kris C WoodDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-5887-2253
Ashutosh ChilkotiDepartment of Biomedical Engineering, Duke University, Durham, NC 27710, USA.ORCID 0000-0002-1569-2228
Duke University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Pharmacological Sciences Training ProgramT32GM007105 · NIGMS · DUKE UNIVERSITY · PI KUHN, CYNTHIA M · 1985 to 2019
$9.0M
ELASTIN FUSION PROTEINSR01GM061232 · NIGMS · DUKE UNIVERSITY · PI CHILKOTI, ASHUTOSH · 2000 to 2017
$4.6M
Thermally Targeted Drug Delivery by Elastin BiopolymersR01EB000188 · NIBIB · DUKE UNIVERSITY · PI CHILKOTI, ASHUTOSH · 2002 to 2015
$3.9M
Selectively targeting apoptosis in PIK3CA mutant colorectal cancersR01CA207083 · NCI · DUKE UNIVERSITY · PI WOOD, KRIS C. · 2016 to 2020
$1.8M
NCI NIH HHS P30 CA014236NCI NIH HHS R01 CA207083NIBIB NIH HHS R01 EB000188NIGMS NIH HHS R01 GM061232NIGMS NIH HHS T32 GM007105
6 · The paper itself

Abstract

Extrinsic pathway agonists have failed repeatedly in the clinic for three core reasons: Inefficient ligand-induced receptor multimerization, poor pharmacokinetic properties, and tumor intrinsic resistance. Here, we address these factors by (i) using a highly potent death receptor agonist (DRA), (ii) developing an injectable depot for sustained DRA delivery, and (iii) leveraging a CRISPR-Cas9 knockout screen in DRA-resistant colorectal cancer (CRC) cells to identify functional drivers of resistance. Pharmacological blockade of XIAP and BCL-X

Indexed as

AnimalsAntineoplastic Agentsbcl-X ProteinColorectal NeoplasmsDelayed-Action PreparationsDrug Resistance, NeoplasmHCT116 CellsHT29 CellsHumansMiceXenograft Model Antitumor AssaysX-Linked Inhibitor of Apoptosis ProteinAntineoplastic AgentsBCL2L1 protein, humanbcl-X ProteinDelayed-Action PreparationsXIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID31517048
PMCPMC6726446
OpenAlexW2971799124

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.