BRD4 inhibition sensitizes aggressive non-Hodgkin lymphomas to PI3Kδ inhibitors by suppressing PI3K reactivation and c-MYC expression.

Weiqiong Zuo, Yongxia Zhu, Zhihao Liu, Yong Xia, Ying Xu, Cuiting Peng, Luoting Yu, Ningyu Wang

Open access · greenAbstract read

In one paragraph

Article in American journal of cancer research, 2021. 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

0.2field-weighted citation impact, top 49% 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, 3 citations in OpenAlex.

B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.Frontiers in pharmacology · 2024
Article
When Just One Phosphate Is One Too Many: The Multifaceted Interplay between Myc and Kinases.International journal of molecular sciences · 2023
Review

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

8 authors at 2 institutions in 1 country.

Weiqiong ZuoState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Yongxia ZhuDepartment of Clinical Pharmacy, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China Chengdu 610041, China.

Zhihao LiuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Yong XiaState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Ying XuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Cuiting PengState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Luoting YuState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Collaborative Innovation Center for Biotherapy Chengdu 610041, China.

Ningyu WangSchool of Life Science and Engineering, Southwest Jiaotong University Chengdu 610031, China.

Sichuan Cancer Hospital · CNSouthwest Jiaotong University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Targeting phosphatidylinositol 3-kinase δ (PI3Kδ) is an important therapeutic strategy for indolent non-Hodgkin lymphomas (NHLs). However, we previously observed reactivation of phosphatidylinositol 3-kinase (PI3K) pathways in aggressive NHL cell lines following continuous exposure to PI3Kδ inhibitors (PI3Kδi), which limited their efficacy and suggests that more studies should be focused on this reactivation to improve current PI3Kδi-based treatments. Herein we conducted a drug synergy screening that combined a marketed PI3Kδi, idelalisib, with 14 well-characterized epigenetic drugs across several types of aggressive NHL cell lines. We identified BRD4 inhibitors (BRD4i) as potent partners that, in combination with idelalisib, were capable of synergistically exerting anti-proliferative activity and inducing cell apoptosis in a panel of aggressive NHL cell lines through continuous suppression of PI3K pathways. More importantly, the combination of BRD4i and PI3Kδi simultaneously inhibited transcription and translation of the oncogenic transcription factor c-MYC, downregulating the expression of c-MYC and continuously suppressing the proliferation of cancer cells

Indexed as

Aggressive NHLBRD4 inhibitorsdrug synergy screeningdrug withdrawalPI3Kδ inhibitors

Identifiers

PMID33520370

PMCPMC7840716

OpenAlexW3127846301

What OpenQuestion holds

Textmetadata

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 OpenQuestion graph.