Evidence map›Paper›PMID 38507740›Full record

ArticleMolecular cancer therapeutics2024

Inhibition of MALT1 and BCL2 Induces Synergistic Antitumor Activity in Models of B-Cell Lymphoma.

Joshua P Plotnik, Adam E Richardson, Haopeng Yang, Estela Rojas, Velitchka Bontcheva, Colleen Dowell, Sydney Parsons, Ashley Wilson, Vida Ravanmehr, Christine Will and 19 more

Abstract read
In one paragraph

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 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

29 authors.

Joshua P PlotnikAbbVie Inc., North Chicago, Illinois.ORCID 0000-0002-0266-9571
Adam E RichardsonAbbVie Inc., North Chicago, Illinois.ORCID 0009-0008-5395-8462
Haopeng YangDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-3870-2679
Estela RojasDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0006-4878-9815
Velitchka BontchevaAbbVie Inc., North Chicago, Illinois.ORCID 0009-0004-2166-644X
Colleen DowellAbbVie Inc., North Chicago, Illinois.ORCID 0009-0004-5339-2121
Sydney ParsonsDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0009-0009-2223-2121
Ashley WilsonDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0003-2949-8466
Vida RavanmehrDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-3971-1083
Christine WillAbbVie Inc., North Chicago, Illinois.ORCID 0009-0006-7667-3043
Paul JungAbbVie Inc., North Chicago, Illinois.ORCID 0000-0001-9168-6738
Haizhong ZhuAbbVie Inc., North Chicago, Illinois.ORCID 0009-0006-7646-0910
Sarathy Karunan ParthaAbbVie Inc., North Chicago, Illinois.ORCID 0009-0000-4836-9147
Sanjay C PanchalAbbVie Inc., North Chicago, Illinois.ORCID 0009-0000-4198-7559
Raghuveer Singh MaliAbbVie Bay Area, South San Francisco, California.ORCID 0009-0003-3010-2868
Frederick J KohlhappAbbVie Inc., North Chicago, Illinois.ORCID 0009-0007-3132-5587
Ryan A McClureAbbVie Inc., North Chicago, Illinois.ORCID 0000-0002-0163-9290
Cyril Y RamathalAbbVie Inc., North Chicago, Illinois.ORCID 0000-0003-0319-9943
Mariam D GeorgeAbbVie Inc., North Chicago, Illinois.ORCID 0009-0006-9898-6219
Manisha JhalaAbbVie Inc., North Chicago, Illinois.ORCID 0009-0001-2913-6441
Nathaniel L ElsenAbbVie Inc., North Chicago, Illinois.ORCID 0000-0003-1192-7242
Wei QiuAbbVie Inc., North Chicago, Illinois.ORCID 0000-0003-0600-1306
Russell A JudgeAbbVie Inc., North Chicago, Illinois.ORCID 0000-0001-5917-9269
Chin PanAbbVie Bay Area, South San Francisco, California.ORCID 0009-0008-2832-8303
Anthony MastracchioAbbVie Inc., North Chicago, Illinois.ORCID 0000-0002-8180-9834
Jared HendersonDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0002-5121-5234
Jonathan A MeulbroekAbbVie Inc., North Chicago, Illinois.ORCID 0009-0000-5322-2844
Michael R GreenDepartment of Lymphoma and Myeloma, University of Texas MD Anderson Cancer Center, Houston, Texas.ORCID 0000-0001-6309-9472
William N PappanoAbbVie Inc., North Chicago, Illinois.ORCID 0000-0003-2848-2219

Funding

AbbVie (Allergan)
6 · The paper itself

Abstract

The activated B cell (ABC) subset of diffuse large B-cell lymphoma (DLBCL) is characterized by chronic B-cell receptor signaling and associated with poor outcomes when treated with standard therapy. In ABC-DLBCL, MALT1 is a core enzyme that is constitutively activated by stimulation of the B-cell receptor or gain-of-function mutations in upstream components of the signaling pathway, making it an attractive therapeutic target. We discovered a novel small-molecule inhibitor, ABBV-MALT1, that potently shuts down B-cell signaling selectively in ABC-DLBCL preclinical models leading to potent cell growth and xenograft inhibition. We also identified a rational combination partner for ABBV-MALT1 in the BCL2 inhibitor, venetoclax, which when combined significantly synergizes to elicit deep and durable responses in preclinical models. This work highlights the potential of ABBV-MALT1 monotherapy and combination with venetoclax as effective treatment options for patients with ABC-DLBCL.

Indexed as

Drug SynergismMucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 ProteinProto-Oncogene Proteins c-bcl-2Xenograft Model Antitumor AssaysAnimalsAntineoplastic AgentsBridged Bicyclo Compounds, HeterocyclicCell Line, TumorCell ProliferationDisease Models, AnimalHumansLymphoma, Large B-Cell, DiffuseMiceSulfonamidesAntineoplastic AgentsBCL2 protein, humanBridged Bicyclo Compounds, HeterocyclicMALT1 protein, humanMucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 ProteinProto-Oncogene Proteins c-bcl-2Sulfonamidesvenetoclax

Identifiers

PMID38507740
PMCPMC11217731

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.