Evidence map›Paper›PMID 35306207›Full record

ArticleSLAS discovery : advancing life sciences R & D2022

Lead identification using 3D models of pancreatic cancer.

Virneliz Fernandez-Vega, Shurong Hou, Dennis Plenker, Hervé Tiriac, Pierre Baillargeon, Justin Shumate, Louis Scampavia, Jan Seldin, Glauco R Souza, David A Tuveson and 1 more

Open access · diamondAbstract read
In one paragraph

Article in SLAS discovery : advancing life sciences R & D, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.4field-weighted citation impact, top 11% 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

16 citing papers in PubMed, 31 citations in OpenAlex.

  1. High throughput screening for SARS-CoV-2 inhibitors targeting 5 helix bundle.SLAS discovery : advancing life sciences R & D · 2025
    Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Protocol for 3D screening of lung cancer spheroids using natural products.SLAS discovery : advancing life sciences R & D · 2023
    Article
  14. Review
  15. Review
  16. Review
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 at 3 institutions in 1 country.

Virneliz Fernandez-VegaThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.
Shurong HouThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.
Dennis PlenkerCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Hervé TiriacUniversity of San Diego, California, Moores Cancer Center, Department of Surgery, San Diego, CA, USA.
Pierre BaillargeonThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.
Justin ShumateThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.
Louis ScampaviaThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA.
Jan SeldinGreiner Bio-One North America, Inc., Monroe, NC, USA.
Glauco R SouzaGreiner Bio-One North America, Inc., Monroe, NC, USA.
David A TuvesonCancer Center, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.
Timothy P SpicerThe Scripps Research Institute Molecular Screening Center, Department of Molecular Medicine, Scripps Florida, Jupiter, FL, USA. Electronic address: spicert@scripps.edu.
Scripps Research Institute · USCold Spring Harbor Laboratory · USUniversity of San Diego · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
Advanced Development and Validation of 3 Dimensional Spheroid Culture of Primary Cancer Cells using Nano3D TechnologyR33CA206949 · NCI · SCRIPPS FLORIDA · PI SPICER, TIMOTHY PATRICK · 2016 to 2019
$1.6M
Integrated Acoustic Transfer System for HTS Library ManagementS10OD025279 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2018 to 2018
$624k
HTS Drug  Discovery DispensersS10OD026857 · OD · SCRIPPS FLORIDA · PI SCAMPAVIA, LOUIS DANIEL · 2019 to 2019
$452k
NCI NIH HHS P30 CA045508NCI NIH HHS R33 CA206949NIH HHS S10 OD025279NIH HHS S10 OD026857
6 · The paper itself

Abstract

Recent technological advances have enabled 3D tissue culture models for fast and affordable HTS. We are no longer bound to 2D models for anti-cancer agent discovery, and it is clear that 3D tumor models provide more predictive data for translation of preclinical studies. In a previous study, we validated a microplate 3D spheroid-based technology for its compatibility with HTS automation. Small-scale screens using approved drugs have demonstrated that drug responses tend to differ between 2D and 3D cancer cell proliferation models. Here, we applied this 3D technology to the first ever large-scale screening effort completing HTS on over 150K molecules against primary pancreatic cancer cells. It is the first demonstration that a screening campaign of this magnitude using clinically relevant, ex-vivo 3D pancreatic tumor models established directly from biopsy, can be readily achieved in a fashion like traditional drug screen using 2D cell models. We identified four unique series of compounds with sub micromolar and even low nanomolar potency against a panel of patient derived pancreatic organoids. We also applied the 3D technology to test lead efficacy in autologous cancer associated fibroblasts and found a favorable profile for better efficacy in the cancer over wild type primary cells, an important milestone towards better leads. Importantly, the initial leads have been further validated in across multiple institutes with concordant outcomes. The work presented here represents the genesis of new small molecule leads found using 3D models of primary pancreas tumor cells.

Indexed as

OrganoidsPancreatic NeoplasmsCell ProliferationHumansHTSMagnetic bioprintingOrganoidPancreatic cancerPhenotypic

Identifiers

PMID35306207
PMCPMC10258910
OpenAlexW4220871191

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.