Evidence map›Paper›PMID 39049606›Full record

ArticleHaematologica2025

Unlocking the therapeutic potential of selective CDK7 and BRD4 inhibition against multiple myeloma cell growth.

Yao Yao, Shuhui Deng, Jessica Fong Ng, Mei Yuan, Chandraditya Chakraborty, Vera JoyWeiler, Nikhil Munshi, Mariateresa Fulciniti

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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.

Yao YaoJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; Blood Disease Institute, Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical University, Xuzhou, China; The Affiliated Hospital of Xuzhou Medical University, Xuzhou.
Shuhui DengJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020.
Jessica Fong NgJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Mei YuanBlood Disease Institute, Key Laboratory of Bone Marrow Stem Cell, Xuzhou Medical University, Xuzhou.
Chandraditya ChakrabortyJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Vera JoyWeilerJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Nikhil MunshiJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; VA Boston Healthcare System, Boston, MA.
Mariateresa FulcinitiJerome Lipper Multiple Myeloma Disease Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. mariateresa_fulciniti@dfci.harvard.edu.

Funding

Targeting Genomic Instability and Evolution in MyelomaP01CA155258 · NCI · DANA-FARBER CANCER INST · PI Nikhil C. Munshi · 2011 to 2026
$32.5M
BLRD VA I01 BX001584NCI NIH HHS P01 CA155258
6 · The paper itself

Abstract

Multiple myeloma (MM) is a plasma cell malignancy that is considered incurable despite the recent therapeutic advances. Effective targeted therapies are, therefore, needed. Our previous studies proved that inhibiting CDK7 impairs the cell cycle and metabolic programs by disrupting E2F1 and MYC transcriptional activities, making it an appealing therapeutic target for MM. Given that CDK7 and BRD4 operate in two distinct regulatory axes in MM, we hypothesized that targeting these two complementary pathways simultaneously would lead to a deeper and more durable response. Indeed, combination therapy had superior activity against MM cell growth and viability, and induced apoptosis to a greater extent than did single-agent therapy in both cell lines and patients' cells. This synergistic activity was also observed in Waldenström macroglobulinemia (WM) cells and with other inhibitors of E2F1 activity. Dual inhibition effectively impaired the MYC and E2F transcriptional programs and MM tumor growth and progression in xenograft animal models, providing evidence for the potential of combination therapy as a therapeutic strategy in MM and WM.

Indexed as

ApoptosisCell Cycle ProteinsCell ProliferationCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesMultiple MyelomaTranscription FactorsXenograft Model Antitumor AssaysAnimalsBromodomain Containing ProteinsCell Line, TumorDisease Models, AnimalDrug SynergismE2F1 Transcription FactorHumansMiceBRD4 protein, humanBromodomain Containing ProteinsCDK7 protein, humanCell Cycle ProteinsCyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesE2F1 Transcription FactorNuclear ProteinsProtein Kinase InhibitorsProto-Oncogene Proteins c-mycTranscription Factors

Identifiers

PMID39049606
PMCPMC11694116

What OpenQuestion holds

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LicenceCC BY-NC
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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.