ArticleScience translational medicine2021
Targeting acute myeloid leukemia dependency on VCP-mediated DNA repair through a selective second-generation small-molecule inhibitor.
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Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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35 citing papers in PubMed, 53 citations in OpenAlex.
- Article
- p97 Inhibition Synergistically Enhances Hypomethylating Therapy through Targeting of PLK1 in Acute Myeloid Leukemia.Cancer research communications · 2026Article
- Nucleophagy removes cytotoxic trapped PARP1.Nature cell biology · 2026Article
- Article
- Targeting proteostasis for cancer therapy: current advances, challenges, and future perspectives.Molecular cancer · 2025Review
- CRISPR screens identify the ATPase VCP as a druggable therapeutic vulnerability in cholangiocarcinoma.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Harnessing p97/VCP: A Transformative AAA+ ATPase Target for Next-Generation Cancer Therapeutics.Cancers · 2025Review
- Article
- VCP's nuclear journey: Initiated by interacting with KPNB1 to repair DNA damage.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- p97 Inhibitors Possessing Antiviral Activity Against SARS-CoV-2 and Low Cytotoxicity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Design and Synthesis of Novel 5,6,7,8-Tetrahydropyrido[2,3-Drug design, development and therapy · 2025Article
- Targeting p97-Npl4 interaction inhibits tumor TNature immunology · 2024Article
- Visualization of the Cdc48 AAA+ ATPase protein unfolding pathway.Nature communications · 2024Article
- Mechanism of allosteric inhibition of human p97/VCP ATPase and its disease mutant by triazole inhibitors.Communications chemistry · 2024Article
- The DNA damage-independent ATM signalling maintains CBP/DOT1L axis in MLL rearranged acute myeloid leukaemia.Oncogene · 2024Article
- Quantitative proteomics reveals CLR interactome in primary human cells.The Journal of biological chemistry · 2024Article
- Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis.Cell death & disease · 2024Article
- Proteomics analysis reveals the differential impact of the p97 inhibitor CB-5083 on protein levels in various cellular compartments of the HL-60 cell line.microPublication biology · 2024Article
- Valosin-Containing Protein (VCP)/p97 Oligomerization.Sub-cellular biochemistry · 2024Review
- Valosin-containing protein (VCP/p97) is prognostically unfavorable in pediatric AML, and negatively correlates with unfolded protein response proteins IRE1 and GRP78: A report from the Children's Oncology Group.Proteomics. Clinical applications · 2023Article
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Authors and funding
36 authors at 6 institutions in 2 countries.
Blandine RouxUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.ORCID 0000-0003-0667-173X
Camille VaganayUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.
Jesse D VargasCleave Therapeutics Inc., San Francisco, CA 94105, USA.ORCID 0000-0002-3671-6778
Gabriela AlexeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-5668-6297
Chaima BenaksasUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.
Bryann PardieuUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.ORCID 0000-0001-7838-3118
Nina FenouilleUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.
Jana M EllegastDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0003-4201-4227
Edyta MalolepszaBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Frank LingUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.ORCID 0000-0001-9408-4345
Gaetano SodaroUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France.ORCID 0000-0002-7363-1124
Linda RossDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0003-4338-4692
Yana PikmanDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-5336-0216
Amy S ConwayDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0003-4583-5127
Yangzhong TangCleave Therapeutics Inc., San Francisco, CA 94105, USA.
Tony WuCleave Therapeutics Inc., San Francisco, CA 94105, USA.
Daniel J AndersonCleave Therapeutics Inc., San Francisco, CA 94105, USA.ORCID 0000-0002-3249-2439
Ronan Le MoigneCleave Therapeutics Inc., San Francisco, CA 94105, USA.ORCID 0000-0002-5181-9468
Han-Jie ZhouCleave Therapeutics Inc., San Francisco, CA 94105, USA.ORCID 0000-0001-5674-8622
Frédéric LucianoIRCAN, INSERM U1081 and CNRS UMR 7284, 06189 Nice, France.ORCID 0000-0001-9253-4998
Christina R HartiganBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.ORCID 0000-0002-6668-2222
Ilene GalinskyDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0002-9158-5061
Daniel J DeAngeloDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.ORCID 0000-0001-7865-2306
Richard M StoneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Patrick AubergerC3M, INSERM U1065, Team Cell Death, Differentiation, Inflammation and Cancer, 06204 Nice, France.
Monica SchenoneBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.ORCID 0000-0002-6456-8768
Steven A CarrBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.ORCID 0000-0002-7203-4299
Josée Guirouilh-BarbatUniversité de Paris, INSERM U1016 and CNRS UMR 8104, Institut Cochin, 75014 Paris, France.ORCID 0000-0002-8845-7333
Bernard LopezUniversité de Paris, INSERM U1016 and CNRS UMR 8104, Institut Cochin, 75014 Paris, France.ORCID 0000-0001-5088-0155
Mehdi KhaledINSERM U1186, Gustave-Roussy Cancer Center, Université Paris-Saclay, 94805 Villejuif, France.ORCID 0000-0002-9880-858X
Kasper LageBroad Institute of Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02142, USA.ORCID 0000-0001-6827-6239
Olivier HermineUniversité de Paris, INSERM U1163 and CNRS 8254, Institut Imagine, Hôpital Necker, APHP, 75015 Paris, France.
Michael T HemannKoch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.ORCID 0000-0001-6776-2163
Alexandre PuissantUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France. lina.benajiba@inserm.fr kimberly_stegmaier@dfci.harvard.edu alexandre.puissant@inserm.fr.ORCID 0000-0002-3997-9282
Kimberly StegmaierDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Boston Children's Hospital, Harvard Medical School, Boston, MA 02215, USA. lina.benajiba@inserm.fr kimberly_stegmaier@dfci.harvard.edu alexandre.puissant@inserm.fr.ORCID 0000-0003-0218-7895
Lina BenajibaUniversité de Paris, INSERM U944 and CNRS UMR 7212, Institut de Recherche Saint Louis, Hôpital Saint Louis, APHP, 75010 Paris, France. lina.benajiba@inserm.fr kimberly_stegmaier@dfci.harvard.edu alexandre.puissant@inserm.fr.ORCID 0000-0001-5440-1115
Centre National de la Recherche Scientifique · FRBroad Institute · USRapt Therapeutics (United States) · USHarvard University · USInserm · FRMassachusetts Institute of Technology · US
Funding
TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI MATTHEW S DAVIDS · 1996 to 2026
$52.5MIntegrating Transforming Approaches to Identify and Target New Vulnerabilities in CancerR35CA210030 · NCI · DANA-FARBER CANCER INST · PI STEGMAIER, KIMBERLY · 2016 to 2022
$7.3MTargeting mitochondrial one carbon folate metabolism for novel T-cell acute lymphoblastic leukemia therapyK08CA222684 · NCI · DANA-FARBER CANCER INST · PI PIKMAN, YANA · 2018 to 2022
$886kNCI NIH HHS K08 CA222684NCI NIH HHS P01 CA066996NCI NIH HHS R35 CA210030
Abstract
The development and survival of cancer cells require adaptive mechanisms to stress. Such adaptations can confer intrinsic vulnerabilities, enabling the selective targeting of cancer cells. Through a pooled in vivo short hairpin RNA (shRNA) screen, we identified the adenosine triphosphatase associated with diverse cellular activities (AAA-ATPase) valosin-containing protein (VCP) as a top stress-related vulnerability in acute myeloid leukemia (AML). We established that AML was the most responsive disease to chemical inhibition of VCP across a panel of 16 cancer types. The sensitivity to VCP inhibition of human AML cell lines, primary patient samples, and syngeneic and xenograft mouse models of AML was validated using
Indexed as
Antineoplastic AgentsLeukemia, Myeloid, AcuteAdenosine TriphosphatasesAnimalsCell Line, TumorDNA RepairHumansMiceValosin Containing ProteinAdenosine TriphosphatasesAntineoplastic AgentsValosin Containing Protein
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