Evidence map›Paper›PMID 39379134›Full record

ArticleBritish journal of haematology2024

Combined MEK1/2 and ATR inhibition promotes myeloma cell death through a STAT3-dependent mechanism in vitro and in vivo.

Lin Li, Xiaoyan Hu, Jewel Nkwocha, Maciej Kmieciak, Mark B Meads, Kenneth H Shain, Raghunandan R Alugubelli, Ariosto S Silva, Hashim Mann, Praneeth R Sudalagunta and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of haematology, 2024. 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
–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

2 citing papers in PubMed.

  1. Article
  2. 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

13 authors.

Lin LiDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Xiaoyan HuDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Jewel NkwochaDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Maciej KmieciakMassey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
Mark B MeadsDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Kenneth H ShainDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Raghunandan R AlugubelliDepartment of Malignant Hematology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Ariosto S SilvaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Hashim MannDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.
Praneeth R SudalaguntaDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Rafael R CanevaroloDepartment of Metabolism and Physiology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA.
Liang ZhouDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID https://orcid.org/0000-0001-5457-7532
Steven GrantDivision of Hematology/Oncology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.ORCID https://orcid.org/0000-0003-4452-9320

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Renato Martins · 1985 to 2026
$51.0M
Princess Margaret Phase I Consorium (PMP1C)UM1CA186644 · NCI · UNIVERSITY HEALTH NETWORK · PI Philippe Bedard, Kevin D Courtney · 2014 to 2026
$16.6M
Targeting Multiple Myeloma with Smac-mimetics and HDAC InhibitorsR01CA205607 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI GRANT, STEVEN · 2016 to 2020
$1.6M
NCI NIH HHS P30 CA016059NCI NIH HHS P30 CA076292NCI NIH HHS R01 CA205607NCI NIH HHS UM1 CA186644NIH/NCI 5UM1CA186644NIH/NCI CA205607NIH/NCI P30 CA16059
6 · The paper itself

Abstract

Mechanisms underlying potentiation of the anti-myeloma (MM) activity of ataxia telangiectasia Rad3 (ATR) antagonists by MAPK (Mitogen-activated protein kinases)-related extracellular kinase 1/2 (MEK1/2) inhibitors were investigated. Co-administration of the ATR inhibitor (ATRi) BAY1895344 (BAY) and MEK1/2 inhibitors, for example, cobimetinib, synergistically increased cell death in diverse MM cell lines. Mechanistically, BAY and cobimetinib blocked STAT3 Tyr705 and Ser727 phosphorylation, respectively, and dual dephosphorylation triggered marked STAT3 inactivation and downregulation of STAT3 (Signal transducer and activator of transcription 3) downstream targets (c-Myc and BCL-X

Indexed as

Ataxia Telangiectasia Mutated ProteinsMAP Kinase Kinase 1Multiple MyelomaSTAT3 Transcription FactorAnimalsAzetidinesCell DeathCell Line, TumorDrug SynergismHumansMAP Kinase Kinase 2MiceMice, SCIDPiperidinesProtein Kinase InhibitorsXenograft Model Antitumor AssaysAtaxia Telangiectasia Mutated ProteinsATR protein, humanAzetidinescobimetinibMAP2K1 protein, humanMAP2K2 protein, humanMAP Kinase Kinase 1MAP Kinase Kinase 2PiperidinesProtein Kinase InhibitorsSTAT3 protein, humanSTAT3 Transcription FactorATR inhibitormultiple myelomaSTAT3

Identifiers

PMID39379134
PMCPMC11650795

What OpenQuestion holds

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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.