Evidence map›Paper›PMID 38429272›Full record

ArticleCell death discovery2024

SOX2 and OCT4 mediate radiation and drug resistance in pancreatic tumor organoids.

Sanjit Roy, Tijana Dukic, Zachery Keepers, Binny Bhandary, Narottam Lamichhane, Jason Molitoris, Young H Ko, Aditi Banerjee, Hem D Shukla

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

13 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
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  5. Tumor organoids modeling reveals timed responses and interplay of radiotherapy and chemotherapy in pancreatic cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2026
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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

9 authors at 1 institution in 1 country.

Sanjit RoyDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Tijana DukicDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Zachery KeepersDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0009-0008-8730-5435
Binny BhandaryDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Narottam LamichhaneDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Jason MolitorisDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Young H KoDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA.
Aditi BanerjeeDepartment of Pediatrics, University of Maryland School of Medicine, Baltimore, MD, USA.
Hem D ShuklaDivision of Translational Radiation Sciences, Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA. hdshukla@som.umaryland.edu.ORCID http://orcid.org/0000-0003-0443-4087
University of Maryland, Baltimore · US

Funding

American Cancer Society (American Cancer Society, Inc.) 10023110
6 · The paper itself

Abstract

Pancreatic cancer has a five-year survival rate of only 10%, mostly due to late diagnosis and limited treatment options. In patients with unresectable disease, either FOLFIRINOX, a combination of 5-fluorouracil (5-FU), oxaliplatin and irinotecan, or gemcitabine plus nab-paclitaxel combined with radiation are frontline standard regimens. However, chemo-radiation therapy has shown limited success because patients develop resistance to chemotherapy and/or radiation. In this study, we evaluated the role of pancreatic cancer stem cells (CSC) using OCT4 and SOX2, CSC markers in mouse pancreatic tumor organoids. We treated pancreatic tumor organoids with 4 or 8 Gy of radiation, 10 μM of 5-FU (5-Fluorouracil), and 100 μM 3-Bromopyruvate (3BP), a promising anti-cancer drug, as a single treatment modalities, and in combination with RT. Our results showed significant upregulation of, OCT4, and SOX2 expression in pancreatic tumor organoids treated with 4 and 8 Gy of radiation, and downregulation following 5-FU treatment. The expression of CSC markers with increasing treatment dose exhibited elevated upregulation levels to radiation and downregulation to 5-FU chemotherapy drug. Conversely, when tumor organoids were treated with a combination of 5-FU and radiation, there was a significant inhibition in SOX2 and OCT4 expression, indicating CSC self-renewal inhibition. Noticeably, we also observed that human pancreatic tumor tissues exhibited heterogeneous and aberrant OCT4 and SOX2 expression as compared to normal pancreas, indicating their potential role in pancreatic cancer growth and therapy resistance. In addition, the combination of 5-FU and radiation treatment exhibited significant inhibition of the β-catenin pathway in pancreatic tumor organoids, resulting in sensitization to treatment and organoid death. In conclusion, our study emphasizes the crucial role of CSCs in therapeutic resistance in PC treatment. We recommend using tumor organoids as a model system to explore the impact of CSCs in PC and identify new therapeutic targets.

Identifiers

PMID38429272
PMCPMC10907757
OpenAlexW4392354541

What OpenQuestion holds

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Registered trials

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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.