Evidence map›Paper›PMID 34201419›Full record

ArticleBiomedicines2021

Multiplex Patient-Based Drug Response Assay in Pancreatic Ductal Adenocarcinoma.

Andrew Armstrong, Muhammad R Haque, Sina Mirbagheri, Usman Barlass, Douglas Z Gilbert, Jaimin Amin, Ajaypal Singh, Ankur Naqib, Faraz Bishehsari

Open access · goldAbstract read
In one paragraph

Article in Biomedicines, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 19% 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, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Engineering Organoids forFrontiers in molecular neuroscience · 2021
    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

9 authors at 1 institution in 1 country.

Andrew ArmstrongDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Muhammad R HaqueDivision of Digestive Diseases, Rush Center for Integrated Microbiome & Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0002-7487-2667
Sina MirbagheriDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Usman BarlassDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Douglas Z GilbertDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Jaimin AminDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Ajaypal SinghDepartment of Internal Medicine, Division of Gastroenterology, Rush University Medical Center, Chicago, IL 60612, USA.
Ankur NaqibDivision of Digestive Diseases, Rush Center for Integrated Microbiome & Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA.ORCID 0000-0003-0832-5646
Faraz BishehsariDivision of Digestive Diseases, Rush Center for Integrated Microbiome & Chronobiology Research, Rush University Medical Center, Chicago, IL 60612, USA.
Rush University Medical Center · US

Funding

Institute for Translational Medicine (ITM) 5UL1TR002389-02
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDA) is an extremely lethal malignancy arising from the pancreas. The treatment of PDA is complicated by ineffective treatments and a lack of biomarkers predictive of treatment success. We have designed a patient-derived organoid (PDO) based high-throughput drug screening assay to model treatment response to a variety of conventional and investigational treatments for PDA. Consecutive patients undergoing endoscopic ultrasound-guided fine-needle biopsy for tissue diagnosis of PDA at Rush University Medical Center were offered to participate in the study. Biopsies were immediately processed to develop organoids. Fifteen PDOs were screened for sensitivity to 18 compounds, including conventional PDA chemotherapies and FDA-approved investigational targeted therapies in cancer using Cell-titer GLO 3D (Promega) cell viability assay. The area under the curve (AUC) was calculated and normalized to the maximum area under the curve to generate a normalized AUC between 0 and 1. Molecular profiling of PDOs was conducted using RNA-seq. Human PDA transcriptomic was extracted from The Cancer Genome Atlas (TCGA). The drug response curves were reproducible. We observed variation in response to conventional therapies overall as well as among individual patients. There were distinct transcriptome signatures associated with response to the conventional chemotherapeutics in PDA. The transcriptomic profile of overall resistance to conventional therapies in our study was associated with poor survival in PDA patients in TCGA. Our pathway analysis for targeted drugs revealed a number of predictors of response associated with the mechanism of action of the tested drug. The multiplex organoid-based drug assay could be used in preclinical to inform patient stratification and therapeutic selection in PDA. When combined with omics data, ex vivo response to treatment could help identify gene signatures associated with response to novel therapies.

Indexed as

drug screeningpancreatic ductal adenocarcinomapatient-derived organoid

Identifiers

PMID34201419
PMCPMC8301364
OpenAlexW3175029244

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.