Evidence map›Paper›PMID 39824957›Full record

ArticleNPJ precision oncology2025

Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.

Brock J Sishc, Janapriya Saha, Elizabeth M Alves, Lianghao Ding, Huiming Lu, Shih-Ya Wang, Katy L Swancutt, James H Nicholson, Angelica Facoetti, Arnold Pompos and 4 more

Abstract read
In one paragraph

Article in NPJ precision oncology, 2025. 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. Article
  2. Review
  3. Article
  4. Review
  5. Review
  6. International journal of particle therapy · 2025
    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

14 authors.

Brock J SishcRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Janapriya SahaRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Elizabeth M AlvesRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Lianghao DingRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Huiming LuRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Shih-Ya WangRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Katy L SwancuttRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.ORCID http://orcid.org/0000-0002-8991-409X
James H NicholsonRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Angelica FacoettiMedical Physics Unit & Research Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy.
Arnold PomposRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Mario CioccaMedical Physics Unit & Research Department, CNAO National Center for Oncological Hadrontherapy, Pavia, Italy.
Todd A AguileraRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Michael D StoryRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. story.michael2@mayo.edu.ORCID http://orcid.org/0000-0001-6522-4169
Anthony J DavisRadiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. anthony.davis@utsouthwestern.edu.ORCID http://orcid.org/0000-0003-0184-3651

Funding

Pathway Choice of DNA Double-Strand Break RepairR01CA162804 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI DAVIS, ANTHONY J · 2012 to 2021
$3.4M
DNA-PKcs and PIDD interaction in DNA damage responseR01CA233594 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI DAVIS, ANTHONY J · 2019 to 2023
$1.8M
NCI NIH HHS R01 CA162804NCI NIH HHS R01 CA233594U.S. Department of Health & Human Services | National Institutes of Health (NIH) CA233594
6 · The paper itself

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response. We utilized a panel of human PDAC cell lines with diverse genetic profiles to determine their sensitivity to CIRT compared to γ-rays, assessing relative biological effectiveness (RBE) at 10% survival, which ranged from 1.96 to 3.04. Increased radiosensitivity was linked to impaired DNA double-strand break (DSB) repair, particularly in cell lines with deficiencies in the homologous recombination (HR) repair pathway and/or elevated genomic instability from replication stress. Furthermore, pretreatment with the HR inhibitor B02 significantly enhanced CIRT sensitivity in a radioresistant PDAC cell line when irradiated in the spread-out Bragg peak but not at the entry position of the beam. These findings suggest that PDAC tumors with HR pathway mutations or high replication stress are more likely to benefit from CIRT while minimizing normal tissue toxicity.

Identifiers

PMID39824957
PMCPMC11742413

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.