Evidence map›Paper›PMID 37886470›Full record

ArticleResearch square2023

Wenge Zhu, Y I Zhang, Shuyan Zhou, Yan Kai, Ya-Qin Zhang, Changmin Peng, Zhuqing Li, Muhammad Mughal, Junfeng Ma, Shunqiang Li and 3 more

Open access · greenAbstract readPreprint
In one paragraph

Article in Research square, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Wenge ZhuSchool of medicine and health science, George Washington University.ORCID 0000-0001-9113-5020
Y I ZhangGeorge Washington University.
Shuyan ZhouSchool of medicine and health science, George Washington University.
Yan KaiSchool of medicine and health science, George Washington University.
Ya-Qin ZhangNational Center for Advancing Translational Sciences.
Changmin PengSchool of medicine and health science, George Washington University.
Zhuqing LiGeorge Washington University.
Muhammad MughalSchool of medicine and health science, George Washington University.
Junfeng MaLombardi Comprehensive Cancer Center, Georgetown University Medical Center.
Shunqiang LiWashington University in St. Louis.
Cynthia MaWashington University in St. Louis.ORCID 0000-0002-8156-7492
Min ShenNIH.
Matthew HallNational Center for Advancing Translational Sciences, National Institutes of Health.ORCID 0000-0002-5073-442X
George Washington University · USNational Institutes of Health · USWashington University in St. Louis · USGeorgetown University · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI Louis M Weiner · 1990 to 2026
$71.5M
The role of And-1 in nucleotide excision repairR01CA258357 · NCI · GEORGE WASHINGTON UNIVERSITY · PI Wenge Zhu · 2022 to 2026
$2.2M
Targeting Fanconi Anemia pathway to overcome platinum drug resistance in ovarian cancerR01CA247684 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2021 to 2025
$2.1M
The Regulation of Cisplatin resistance in ovarian cancerR01CA184717 · NCI · GEORGE WASHINGTON UNIVERSITY · PI ZHU, WENGE · 2014 to 2018
$1.6M
NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA184717NCI NIH HHS R01 CA247684NCI NIH HHS R01 CA258357
6 · The paper itself

Abstract

Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle and cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to CDK4/6 inhibitors (CDK4/6i), such as palbociclib, remains a substantial challenge in clinical settings. Using high-throughput combinatorial drug screening and genomic sequencing, we found that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase (OGT) in palbociclib-resistant breast cancer cells and tumors; O-GlcNAcylation of MITF at Serine 49 enhanced its interaction with importin α/β, thus promoting its translocation to nuclei, where it suppressed palbociclib-induced senescence; inhibition of MITF or its O-GlcNAcylation re-sensitized resistant cells to palbociclib. Remarkably, clinical studies confirmed the activation of MITF in tumors from patients who are palbociclib-resistant or undergoing palbociclib treatment. Collectively, our studies shed light on a novel mechanism regulating palbociclib-resistance, and present clinical evidence for developing therapeutic approaches to treat CDK4/6i-resistant breast cancer patients.

Identifiers

PMID37886470
PMCPMC10602086
OpenAlexW4387301381

What OpenQuestion holds

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LicenceCC BY
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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 OpenQuestion graph.