Evidence map›Paper›PMID 39235982›Full record

ArticleJCI insight2024

ATR inhibition radiosensitizes cells through augmented DNA damage and G2 cell cycle arrest abrogation.

Scott J Bright, Mandira Manandhar, David B Flint, Rishab Kolachina, Mariam Ben Kacem, David Kj Martinus, Broderick X Turner, Ilsa Qureshi, Conor H McFadden, Poliana C Marinello and 2 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Review
  2. Article
  3. DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 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

12 authors.

Scott J BrightDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mandira ManandharDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
David B FlintDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Rishab KolachinaDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Mariam Ben KacemDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
David Kj MartinusDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Broderick X TurnerDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Ilsa QureshiDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Conor H McFaddenDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Poliana C MarinelloDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Simona F ShaitelmanDepartment of Immunology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gabriel O SawakuchiDepartment of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Project 3: Enhanced Sensitivity of Tumors to Proton Beam Therapy: Mechanisms and Biomarkers.P01CA261669 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI TITT, UWE · 2021 to 2025
$14.0M
Alpha particles combined with ATR inhibition to activate the immune system: mechanisms and pre-clinical translationR01CA279119 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Gabriel Oliveira Sawakuchi · 2023 to 2026
$2.1M
Augmenting Anti-Tumor Immunity Using Radiation in the Setting of DNA Repair DefectsR21CA252411 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI SAWAKUCHI, GABRIEL OLIVEIRA, SHAITELMAN, SIMONA · 2020 to 2020
$431k
NCI NIH HHS P01 CA261669NCI NIH HHS P30 CA016672NCI NIH HHS R01 CA279119NCI NIH HHS R21 CA252411
6 · The paper itself

Abstract

Ataxia telangiectasia and Rad3-related protein (ATR) is a key DNA damage response protein that facilitates DNA damage repair and regulates cell cycle progression. As such, ATR is an important component of the cellular response to radiation, particularly in cancer cells, which show altered DNA damage response and aberrant cell cycle checkpoints. Therefore, ATR's pharmacological inhibition could be an effective radiosensitization strategy to improve radiotherapy. We assessed the ability of an ATR inhibitor, AZD6738, to sensitize cancer cell lines of various histologic types to photon and proton radiotherapy. We found that radiosensitization took place through persistent DNA damage and abrogated G2 cell cycle arrest. We also found that AZD6738 increased the number of micronuclei after exposure to radiotherapy. We found that combining radiation with AZD6738 led to tumor growth delay and prolonged survival relative to radiation alone in a breast cancer model. Combining AZD6738 with photons or protons also led to increased macrophage infiltration at the tumor microenvironment. These results provide a rationale for further investigation of ATR inhibition in combination with radiotherapy and with other agents such as immune checkpoint blockade.

Indexed as

Ataxia Telangiectasia Mutated ProteinsDNA DamageG2 Phase Cell Cycle CheckpointsRadiation-Sensitizing AgentsAnimalsBreast NeoplasmsCell Line, TumorFemaleHumansIndolesMiceMorpholinesPyrazolesPyrimidinesRadiation ToleranceSulfonamidesAtaxia Telangiectasia Mutated ProteinsATR protein, humanceralasertibIndolesMorpholinesPyrazolesPyrimidinesRadiation-Sensitizing AgentsSulfonamidesSulfoxidesCell cycleDNA repairOncologyRadiation therapy

Identifiers

PMID39235982
PMCPMC11466186

What OpenQuestion holds

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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.