Article in Molecular cancer therapeutics, 2024. 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
0.4field-weighted citation impact, top 38% of its field
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, 2 citations in OpenAlex.
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
28 authors at 6 institutions in 2 countries.
Marissa L CalbertDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0003-3005-8679
Gurushankar ChandramoulyDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0002-4258-9859
Clare M AdamsDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0002-9940-3795
Magali Saez-AyalaCentre de Recherche en Cancérologie de Marseille (CRCM), CNRS, INSERM, Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille, France.ORCID 0000-0002-8726-0053
Tatiana KentDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0001-8237-0184
Mrityunjay TyagiDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0001-7758-5025
V S S Abhinav AyyadevaraFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0003-2085-2588
John GordonMoulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, Pennsylvania.ORCID 0000-0001-8191-2156
Jessica AtkinsFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0002-9563-3358
Monika M TomaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0001-8414-253X
Stéphane BetziCentre de Recherche en Cancérologie de Marseille (CRCM), CNRS, INSERM, Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille, France.ORCID 0000-0001-5935-5058
Andrew S BoghossianBroad Institute of MIT and Harvard, Cambridge Massachusetts.ORCID 0000-0002-7008-8138
Ramkrishna MitraDivision of Biostatistics, Department of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0002-6181-9066
Wayne E ChildersMoulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, Pennsylvania.ORCID 0000-0003-0527-3684
Xavier GrañaFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0001-7134-0473
Tomasz SkorskiFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0002-3809-4538
Christian HurtzFels Cancer Institute for Personalized Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.ORCID 0000-0001-8346-190X
Xavier MorelliCentre de Recherche en Cancérologie de Marseille (CRCM), CNRS, INSERM, Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille, France.ORCID 0000-0001-8101-7901
Christine M EischenDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0003-4618-8996
Richard T PomerantzDepartment of Biochemistry and Molecular Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.ORCID 0000-0003-1194-9871
Sidney Kimmel Cancer Center · USTemple University · USBroad Institute · USCentre National de la Recherche Scientifique · FRFox Chase Cancer Center · USThe Wistar Institute · US
Funding
X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Claudio Guillermo Giraudo · 1995 to 2026
$94.8M
Tumor Microenvironment and MetastasisP30CA010815 · NCI · WISTAR INSTITUTE · PI Aaron Robert Goldman · 1985 to 2026
$75.9M
Compensatory Mechanisms that Promote Homologous Recombination in BRCA1 Mutant CancersR01CA214799 · NCI · RESEARCH INST OF FOX CHASE CAN CTR · PI Neil Johnson · 2017 to 2026
$4.3M
BCLW in lymphoma survival and resistance to targeted BCL2 family therapiesR01CA236853 · NCI · THOMAS JEFFERSON UNIVERSITY · PI EISCHEN, CHRISTINE M. · 2020 to 2025
$2.1M
Dissecting BRCA1-PALB2 Activity in DNA Repair and DevelopmentR01GM135293 · NIGMS · RESEARCH INST OF FOX CHASE CAN CTR · PI JOHNSON, NEIL · 2020 to 2023
$1.9M
A Next-Generation Nucleoside Prodrug for Diffuse Large B-Cell LymphomaR01CA279364 · NCI · THOMAS JEFFERSON UNIVERSITY · PI CHRISTINE M. EISCHEN, Richard T Pomerantz · 2024 to 2026
$1.9M
Targeting Kinase Inhibitor Induced Signaling Plasticity in Patients with Ph-Like ALLK22CA251649 · NCI · TEMPLE UNIV OF THE COMMONWEALTH · PI HURTZ, CHRISTIAN · 2022 to 2024
Anticancer nucleosides are effective against solid tumors and hematologic malignancies, but typically are prone to nucleoside metabolism resistance mechanisms. Using a nucleoside-specific multiplexed high-throughput screening approach, we discovered 4'-ethynyl-2'-deoxycytidine (EdC) as a third-generation anticancer nucleoside prodrug with preferential activity against diffuse large B-cell lymphoma (DLBCL) and acute lymphoblastic leukemia (ALL). EdC requires deoxycytidine kinase (DCK) phosphorylation for its activity and induces replication fork arrest and accumulation of cells in S-phase, indicating it acts as a chain terminator. A 2.1Å cocrystal structure of DCK bound to EdC and UDP reveals how the rigid 4'-alkyne of EdC fits within the active site of DCK. Remarkably, EdC was resistant to cytidine deamination and SAMHD1 metabolism mechanisms and exhibited higher potency against ALL compared with FDA-approved nelarabine. Finally, EdC was highly effective against DLBCL tumors and B-ALL in vivo. These data characterize EdC as a preclinical nucleoside prodrug candidate for DLBCL and ALL.
Indexed as
DeoxycytidineAnimalsCell Line, TumorDeoxycytidine KinaseHumansLeukemiaLymphomaMiceXenograft Model Antitumor AssaysDeoxycytidineDeoxycytidine Kinase
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.
4'-Ethynyl-2'-Deoxycytidine (EdC) Preferentially Targets Lymphoma and Leukemia Subtypes by Inducing Replicative Stress. · full record | OpenQuestion