Evidence map›Paper›PMID 40595495›Full record

ArticleNature communications2025

Identification of the Notch ligand DLK1 as an immunotherapeutic target and regulator of tumor cell plasticity and chemoresistance in adrenocortical carcinoma.

Nai-Yun Sun, Suresh Kumar, Yoo Sun Kim, Diana Varghese, Arnulfo Mendoza, Rosa Nguyen, Reona Okada, Karlyne Reilly, Brigitte Widemann, Yves Pommier and 18 more

Abstract readClinical Trial, Phase I
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 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. DLK1: a novel therapeutic target in cancer.Endocrine-related cancer · 2026
    Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

28 authors.

Nai-Yun SunDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-5401-4104
Suresh KumarDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Yoo Sun KimDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Diana VargheseDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Arnulfo MendozaPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Rosa NguyenPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-5143-2055
Reona OkadaPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-2584-3026
Karlyne ReillyPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0001-9109-4409
Brigitte WidemannPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9198-7175
Yves PommierDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-3108-0758
Fathi ElloumiDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Anjali DhallDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Daiki TaniyamaDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Mayank PatelLaboratory of Pathology, Center for Cancer Research, NCI, Bethesda, MD, USA.
Etan AberPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Cristina F ContrerasPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Rosandra N KaplanPediatric Oncology Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Katja Kiseljak-VassiliadesDepartment of Medicine-Endocrinology/Metabolism/Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0003-3341-582X
Margaret E WiermanDepartment of Medicine-Endocrinology/Metabolism/Diabetes, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Dan MartinezDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jennifer PogorilerDepartment of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia and Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-9366-4401
Amber K HamiltonDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Sharon J DiskinDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, PA, USA.
John M MarisDepartment of Pediatrics, Perelman School of Medicine, University of Pennsylvania, and Children's Hospital of Philadelphia, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-8088-7929
Robert W RobeyLaboratory of Cell Biology, Center for Cancer Research, NCI, Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-0857-3650
Michael M GottesmanLaboratory of Cell Biology, Center for Cancer Research, NCI, Bethesda, MD, USA.
Jaydira Del RiveroDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA.
Nitin RoperDevelopmental Therapeutics Branch, Center for Cancer Research, NCI, Bethesda, MD, USA. nitin.roper@nih.gov.

Funding

Discovering mechanisms of neuroblastoma tumorigenesis to improve patient outcomesR35CA220500 · NCI · CHILDREN'S HOSP OF PHILADELPHIA · PI JOHN M MARIS · 2017 to 2026
$8.7M
Epigenetic and immunologic aspects of neuroendocrine cancersZIABC011989 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI ROPER, NITIN · 2020 to 2025
$5.8M
Intramural NIH HHS ZIA BC011989NCI NIH HHS R35 CA220500
6 · The paper itself

Abstract

While immunotherapeutic targeting of cell surface proteins is an increasingly effective cancer therapy, identification of new surface proteins, particularly those with biological importance, is critical. Here, we uncover delta-like non-canonical Notch ligand 1 (DLK1) as a cell surface protein with limited normal tissue expression and high expression in multiple refractory adult metastatic cancers including small cell lung cancer (SCLC) and adrenocortical carcinoma (ACC), a rare cancer with few effective therapies. In ACC, ADCT-701, a DLK1 targeting antibody-drug conjugate (ADC), shows in vitro and in vivo activity but is overall limited due to high expression and activity of the drug efflux protein ABCB1 (MDR1, P-glycoprotein). In contrast, ADCT-701 induces complete responses in DLK1

Indexed as

Adrenal Cortex NeoplasmsAdrenocortical CarcinomaCalcium-Binding ProteinsDrug Resistance, NeoplasmImmunoconjugatesIntercellular Signaling Peptides and ProteinsMembrane ProteinsAnimalsATP Binding Cassette Transporter, Subfamily BCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansImmunotherapyLung NeoplasmsMiceABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BCalcium-Binding ProteinsDLK1 protein, humanDlk1 protein, mouseImmunoconjugatesIntercellular Signaling Peptides and ProteinsMembrane ProteinsReceptor, Notch1

Identifiers

PMID40595495
PMCPMC12216638

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.