Evidence map›Paper›PMID 39626673›Full record

ArticleCell reports. Medicine2024

UBA1 inhibition sensitizes cancer cells to PARP inhibitors.

Sharad Awasthi, Lacey E Dobrolecki, Christina Sallas, Xudong Zhang, Yang Li, Sima Khazaei, Sumanta Ghosh, Collene R Jeter, Jinsong Liu, Gordon B Mills and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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

11 citing papers in PubMed.

  1. Review
  2. Review
  3. Therapeutic synergies that overcome carboplatin resistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2026
    Article
  4. Review
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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

18 authors.

Sharad AwasthiDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: sawasthi@mdanderson.org.
Lacey E DobroleckiLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Christina SallasLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Xudong ZhangDepartment of Anatomic Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Yang LiDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sima KhazaeiDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Sumanta GhoshDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Collene R JeterDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Jinsong LiuDepartment of Anatomic Pathology, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Gordon B MillsDivision of Oncological Science, Knight Cancer Institute, Oregon Health and Sciences University, Portland, OR 97201, USA.
Shannon N WestinDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Michael T LewisLester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
Weiyi PengDepartment of Biology and Biochemistry, University of Houston, Houston, TX, USA.
Anil K SoodDepartment of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Timothy A YapDepartment of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
S Stephen YiLivestrong Cancer Institutes, Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA; Interdisciplinary Life Sciences Graduate Programs (ILSGP), College of Natural Sciences, The University of Texas at Austin, Austin, TX, USA; Oden Institute for Computational Engineering and Sciences (ICES), The University of Texas at Austin, Austin, TX, USA; Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA.
Daniel J McGrailCenter for Immunotherapy and Precision Immuno-Oncology, Cleveland Clinic, Cleveland, OH, USA; Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. Electronic address: mcgraid@ccf.org.
Nidhi SahniDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Quantitative and Computational Biosciences Program, Baylor College of Medicine, Houston, TX, USA.

Funding

The University of Texas MD Anderson Cancer Center SPORE in Ovarian CancerP50CA281701 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI ROBERT C BAST, ANIL K SOOD · 2023 to 2026
$11.5M
NCI NIH HHS P50 CA281701
6 · The paper itself

Abstract

Therapeutic strategies targeting the DNA damage response, such as poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi), have revolutionized cancer treatment in tumors deficient in homologous recombination (HR). However, overcoming innate and acquired resistance to PARPi remains a significant challenge. Here, we employ a genome-wide CRISPR knockout screen and discover that the depletion of ubiquitin-activating enzyme E1 (UBA1) enhances sensitivity to PARPi in HR-proficient ovarian cancer cells. We show that silencing or pharmacological inhibition of UBA1 sensitizes multiple cell lines and organoid models to PARPi. Mechanistic studies uncover that UBA1 inhibition not only impedes HR repair to sensitize cells to PARP inhibition but also increases PARylation, which may subsequently be targeted by PARP inhibition. In vivo experiments using patient-derived xenografts demonstrate that combining PARP and UBA1 inhibition provided significant survival benefit compared to individual therapies with no detectable signs of toxicity, establishing this combination approach as a promising strategy to extend PARPi benefit.

Indexed as

Poly(ADP-ribose) Polymerase InhibitorsUbiquitin-Activating EnzymesAnimalsCell Line, TumorCRISPR-Cas SystemsDNA DamageFemaleHumansMiceOvarian NeoplasmsPoly(ADP-ribose) PolymerasesXenograft Model Antitumor AssaysPoly(ADP-ribose) Polymerase InhibitorsPoly(ADP-ribose) PolymerasesUBA1 protein, humanUbiquitin-Activating Enzymesbreast cancerhomologous recombination repairovarian cancerPARP inhibitorsubiquitination

Identifiers

PMID39626673
PMCPMC11722100

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.