Evidence map›Paper›PMID 40300249›Full record

ArticleMolecular cancer therapeutics2025

Efficacy of ATR Kinase Inhibitor Elimusertib Monotherapy or Combination in Tumors with DNA Damage Response Pathway and Other Genomic Alterations.

Kaushik Varadarajan, Christian X Cruz Pico, Kurt W Evans, Maria Gabriela Raso, Yasmeen Qamar Rizvi, Xiaofeng Zheng, Dhruv Chachad, Timothy P DiPeri, Bailiang Wang, Stephen M Scott and 5 more

Abstract read
In one paragraph

Article in Molecular cancer therapeutics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. 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

15 authors.

Kaushik VaradarajanDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-4114-5498
Christian X Cruz PicoDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-5620-7727
Kurt W EvansDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0008-6823-6809
Maria Gabriela RasoDepartment of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-2105-5556
Yasmeen Qamar RizviDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0000-2719-4093
Xiaofeng ZhengDepartment of Bioinformatics AND Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0007-2171-7210
Dhruv ChachadDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-3131-7679
Timothy P DiPeriDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-1190-1640
Bailiang WangDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0006-6851-5985
Stephen M ScottDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0002-2910-4287
Ming ZhaoDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0005-9985-4448
Argun AkcakanatDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-4012-9840
Antje M WengnerResearch and Development Oncology, Bayer AG, Leverkusen, Germany.ORCID 0009-0009-5772-1945
Timothy A YapDepartment of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-2154-3309
Funda Meric-BernstamDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-6816-6072

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Convalescent Plasma to Limit Coronavirus Associated ComplicationsUL1TR003167 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KARP, DANIEL D, MCPHERSON, DAVID D · 2019 to 2023
$45.3M
TRAINING OF ACADEMIC SURGICAL ONCOLOGISTST32CA009599 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Ashley M Holder, Jennifer A. Wargo · 1988 to 2026
$13.2M
University of Texas PDX Development and Trial CenterU54CA224065 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAMODARAN, SENTHILKUMAR, MERIC-BERNSTAM, FUNDA · 2017 to 2022
$7.7M
Barr Foundation (BF)MD Anderson Cancer MoonshotNational Center for Advancing Translational Sciences (NCATS) 1UL1TR003167National Institutes of Health (NIH) CA009599NCATS NIH HHS UL1 TR003167NCI NIH HHS P30 CA016672NCI NIH HHS T32 CA009599NCI NIH HHS U54 CA224065Nellie B. Connally Breast Cancer Research EndowmentPDX Development and Trial Center U45 #CA224065Sheikh Khalifa Bin Zayed Al Nahyan Institute for Personalized Cancer Therapy (Khalifa Institute)
6 · The paper itself

Abstract

The ataxia telangiectasia and RAD3-related (ATR) kinase functions with ataxia telangiectasia-mutated (ATM) kinase as a modulator of DNA damage response (DDR). We assessed the antitumor effects of the ATR inhibitor elimusertib (BAY-1895344) in patient-derived xenograft (PDX) models with DDR alterations. Antitumor activity was assessed by change in tumor volume (TV) from baseline. Responses were categorized as follows: partial response (PR), ≥30% decrease in TV; ≥20% increase in TV, progressive disease; and non-PR/progressive disease, stable disease (SD). Event-free survival was defined as time for tumor doubling (EFS-2). Of 21 PDX models tested, 11 had significant prolongation of EFS-2 with elimusertib monotherapy. Four models had a PR and four had SD. PR/SD was observed in two of five models with ATM loss on IHC and in models with a variety of alterations in DDR genes, including BRCA1/2 and ATM. Elimusertib prolonged EFS-2 in three of five models with known PARP inhibitor resistance. Pharmacodynamic studies conducted in four PDX models showed an increase in DNA damage markers. PI3K/mTOR pathway signaling increased in two of four models. The combination of the PI3K inhibitor copanlisib with elimusertib enhanced EFS-2 compared with monotherapy in three of 11 models tested. The combination of elimusertib with the PARP inhibitor niraparib enhanced antitumor activity compared with single agents in PARP-resistant PDX models. Our study shows that ATR inhibition has antitumor activity, including in models with both intrinsic and acquired PARP inhibitor resistance. Further work is needed to better refine patient selection for ATR-based therapies.

Indexed as

Ataxia Telangiectasia Mutated ProteinsDNA DamageNeoplasmsProtein Kinase InhibitorsAnimalsCell Line, TumorFemaleHumansMiceXenograft Model Antitumor AssaysAtaxia Telangiectasia Mutated ProteinsATR protein, humanProtein Kinase Inhibitors

Identifiers

PMID40300249
PMCPMC12402799

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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.