Evidence map›Paper›PMID 34890975›Full record

ArticleBiomaterials2022

Integrated genome and tissue engineering enables screening of cancer vulnerabilities in physiologically relevant perfusable ex vivo cultures.

Michael Hu, Xin Yi Lei, Jon D Larson, Melissa McAlonis, Kyle Ford, Daniella McDonald, Krystal Mach, Jessica M Rusert, Robert J Wechsler-Reya, Prashant Mali

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2022. 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
0.5field-weighted citation impact, top 39% 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, 8 citations in OpenAlex.

  1. 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

10 authors at 3 institutions in 1 country.

Michael HuDepartment of Bioengineering, University of California San Diego, La Jolla, USA.
Xin Yi LeiDepartment of Bioengineering, University of California San Diego, La Jolla, USA.
Jon D LarsonTumor Initiation & Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA.
Melissa McAlonisLudwig Institute for Cancer Research, La Jolla, USA.
Kyle FordDepartment of Bioengineering, University of California San Diego, La Jolla, USA.
Daniella McDonaldBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, USA.
Krystal MachDepartment of Biological Sciences, University of California San Diego, La Jolla, USA.
Jessica M RusertBiomedical Sciences Graduate Program, University of California San Diego, La Jolla, USA.
Robert J Wechsler-ReyaTumor Initiation & Maintenance Program, NCI-Designated Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, USA.
Prashant MaliDepartment of Bioengineering, University of California San Diego, La Jolla, USA. Electronic address: pmali@ucsd.edu.
University of California San Diego · USSanford Burnham Prebys Medical Discovery Institute · USLudwig Cancer Research · US

Funding

Tumor Microenvironment and Cancer ImmunologyP30CA030199 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI ELENA B PASQUALE · 1985 to 2026
$107.2M
Using Networks to Seed Hierarchical Whole-cell Models of CancerU54CA209891 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2017 to 2021
$10.9M
Mouse models to discover new drivers of medulloblastomaR01CA159859 · NCI · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI Michael D. Taylor, WILLIAM A WEISS · 2011 to 2026
$10.4M
U of Calif, San Diego Neuroscience Microscopy ImagingP30NS047101 · NINDS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GLEESON, JOSEPH G, ZHENG, BINHAI · 2003 to 2022
$9.0M
Next-generation Functional Genetic Screening of Un-screenable TraitsR01HG009285 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT, TAMAYO, PABLO · 2017 to 2020
$4.2M
Systematic mapping of genetic vulnerabilities in head and neck cancerR01CA222826 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2022
$1.8M
Dissecting the interplay of gene regulatory networks and cellular niche on cell fate determinationR01GM123313 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MALI, PRASHANT · 2018 to 2021
$1.2M
NCI NIH HHS P30 CA030199NCI NIH HHS R01 CA159859NCI NIH HHS R01 CA222826NCI NIH HHS U54 CA209891NHGRI NIH HHS R01 HG009285NIGMS NIH HHS R01 GM123313NINDS NIH HHS P30 NS047101
6 · The paper itself

Abstract

Genetic screens are powerful tools for both resolving biological function and identifying potential therapeutic targets, but require physiologically accurate systems to glean biologically useful information. Here, we enable genetic screens in physiologically relevant ex vivo cancer tissue models by integrating CRISPR-Cas-based genome engineering and biofabrication technologies. We first present a novel method for generating perfusable tissue constructs, and validate its functionality by using it to generate three-dimensional perfusable dense cultures of cancer cell lines and sustain otherwise ex vivo unculturable patient-derived xenografts. Using this system we enable large-scale CRISPR screens in perfused tissue cultures, as well as emulate a novel point-of-care diagnostics scenario of a clinically actionable CRISPR knockout (CRISPRko) screen of genes with FDA-approved drug treatments in ex vivo PDX cell cultures. Our results reveal differences across in vitro and in vivo cancer model systems, and highlight the utility of programmable tissue engineered models for screening therapeutically relevant cancer vulnerabilities.

Indexed as

NeoplasmsTissue EngineeringCRISPR-Cas SystemsEarly Detection of CancerGenomeHumansBioprintingBreast cancer modelCRISPR screensMedulloblastoma modelPoint-of-care functional screens

Identifiers

PMID34890975
PMCPMC9328412
OpenAlexW3216907422

What OpenQuestion holds

Textmetadata
LicenceTDM
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.