Evidence map›Paper›PMID 30970263›Full record

ArticleCell reports2019

High-Complexity shRNA Libraries and PI3 Kinase Inhibition in Cancer: High-Fidelity Synthetic Lethality Predictions.

Marsilius Mues, Laila Karra, Damia Romero-Moya, Anica Wandler, Matthew J Hangauer, Olga Ksionda, Yvonne Thus, Marthe Lindenbergh, Kevin Shannon, Michael T McManus and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 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
–field-weighted citation impact
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.

  1. Review
  2. Development of constitutively synergistic nanoformulations to enhance chemosensitivity in T-cell leukemia.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Article
  3. Article
  4. Overexpression of ROCK1 promotes cancer cell proliferation and is associated with poor prognosis in human urothelial bladder cancer.Mammalian genome : official journal of the International Mammalian Genome Society · 2021
    Article
  5. Review
  6. Article
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

11 authors.

Marsilius MuesDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Laila KarraDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Damia Romero-MoyaDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Anica WandlerDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Matthew J HangauerDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Olga KsiondaDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Yvonne ThusDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Marthe LindenberghDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA.
Kevin ShannonDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA.
Michael T McManusDiabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
Jeroen P RooseDepartment of Anatomy, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jeroen.roose@ucsf.edu.

Funding

Selectively Targeting Oncogenic NRAS in CancerR01CA193994 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KEVIN M. SHANNON · 2015 to 2026
$5.8M
The Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2M
Balanced signaling cues to guide cell transitions in the blood lineage continuumR01HL120724 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAKRABORTY, ARUP K., NOLAN, GARRY P · 2015 to 2019
$3.7M
Molecular understanding of leukemic bone marrow cytokine-Ras signals and metabolic dependenceR01CA187318 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2015 to 2026
$3.6M
Functional Networks for Persister Cell SensitivitiesR01CA212767 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCMANUS, MICHAEL T · 2017 to 2021
$2.6M
NCI NIH HHS R01 CA187318NCI NIH HHS R01 CA193994NCI NIH HHS R01 CA212767NCI NIH HHS U01 CA217882NHLBI NIH HHS R01 HL120724
6 · The paper itself

Abstract

Deregulated signal transduction is a cancer hallmark, and its complexity and interconnectivity imply that combination therapy should be considered, but large data volumes that cover the complexity are required in user-friendly ways. Here, we present a searchable database resource of synthetic lethality with a PI3 kinase signal transduction inhibitor by performing a saturation screen with an ultra-complex shRNA library containing 30 independent shRNAs per gene target. We focus on Ras-PI3 kinase signaling with T cell leukemia as a screening platform for multiple clinical and experimental reasons. Our resource predicts multiple combination-based therapies with high fidelity, ten of which we confirmed with small molecule inhibitors. Included are biochemical assays, as well as the IPI145 (duvelisib) inhibitor. We uncover the mechanism of synergy between the PI3 kinase inhibitor GDC0941 (pictilisib) and the tubulin inhibitor vincristine and demonstrate broad synergy in 28 cell lines of 5 cancer types and efficacy in preclinical leukemia mouse trials.

Indexed as

AnimalsDisease Models, AnimalHumansMiceNeoplasmsProtein Kinase InhibitorsRNA, Small InterferingSignal TransductionSynthetic Lethal MutationsProtein Kinase InhibitorsRNA, Small InterferingcancerGDC0941inhibitorsleukemiaPI3 kinasepreclinical mouse trialsscreenshRNAsignaling pathwayssynthetic lethalityvincristine

Identifiers

PMID30970263
PMCPMC6690758

What OpenQuestion holds

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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.