Evidence map›Paper›PMID 39939315›Full record

ArticleNature communications2025

High-throughput screening identifies Aurora kinase B as a critical therapeutic target for Merkel cell carcinoma.

Tara Gelb, Khalid A Garman, Daniel Urban, Amy Coxon, Berkley Gryder, Natasha T Hill, Lingling Miao, Tobie Lee, Olivia Lee, Sirisha Chakka and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. Article
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

22 authors.

Tara Gelb *Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0003-1811-8448
Khalid A Garman *Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Daniel UrbanNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Amy CoxonDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Berkley GryderGenetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0000-0003-0130-2302
Natasha T HillDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Lingling MiaoDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Tobie LeeNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Olivia LeeNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0001-5389-6267
Sirisha ChakkaNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
John BraistedNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Jordan E JarvisDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.ORCID http://orcid.org/0009-0001-7551-3447
Rachael GlavinDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Trisha S RajDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Ying XiaoDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
Simone DifilippantonioLaboratory of Animal Sciences Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, 21702, USA.
Amy Q WangNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Min ShenNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Ken Chih-Chien ChengNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Madhu Lal-NagNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.
Matthew D HallNational Center for Advancing Translational Sciences, National Institutes of Health, Rockville, MD, 20850, USA.ORCID http://orcid.org/0000-0002-5073-442X
Isaac BrownellDermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. isaac.brownell@nih.gov.ORCID http://orcid.org/0000-0002-0090-9914

Funding

Molecular pathogenesis and therapy innovation for Merkel cell carcinomaZIAAR041222 · NIAMS · NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES · PI BROWNELL, ISAAC · 2022 to 2025
$4.0M
CCR NIH HHS HHSN261200800001CIntramural NIH HHS ZIA AR041222NCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer. Most MCCs contain Merkel cell polyomavirus (virus-positive MCC; VP-MCC), and the remaining are virus-negative (VN-MCC). Immune checkpoint inhibitors are the first-line treatment for metastatic MCC, but durable responses are achieved in less than 50% of patients. To identify new treatments, we screen ~4,000 compounds for their ability to reduce MCC viability and demonstrate that VP-MCC and VN-MCC exhibit distinct response profiles. Aurora kinase inhibitors selectively reduce VP-MCC viability, with RNAi screening independently identifying AURKB as an essential gene for MCC survival, especially in VP-MCC. AZD2811, a selective AURKB inhibitor, induces mitotic dysregulation and apoptosis in MCC cells, with greater efficacy in VP-MCC. In mice, AZD2811 nanoparticles inhibit tumor growth and increase survival in both VP-MCC and VN-MCC xenograft models. Overall, our unbiased screens identify AURKB as a promising therapeutic target and AZD2811NP as a potential treatment for MCC.

Indexed as

Aurora Kinase BCarcinoma, Merkel CellProtein Kinase InhibitorsSkin NeoplasmsAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell SurvivalFemaleHigh-Throughput Screening AssaysHumansMerkel cell polyomavirusMiceXenograft Model Antitumor AssaysAntineoplastic AgentsAURKB protein, humanAurora Kinase BProtein Kinase Inhibitors

Identifiers

PMID39939315
PMCPMC11822212

What OpenQuestion holds

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LicenceCC BY
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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.