Evidence map›Paper›PMID 37356470›Full record

ArticleCancer letters2023

Drug combinations identified by high-throughput screening promote cell cycle transition and upregulate Smad pathways in myeloma.

Tyler J Peat, Snehal M Gaikwad, Wendy Dubois, Nana Gyabaah-Kessie, Shuling Zhang, Sayeh Gorjifard, Zaw Phyo, Megan Andres, V Keith Hughitt, R Mark Simpson and 22 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. 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

32 authors at 10 institutions in 1 country.

Tyler J PeatLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA. Electronic address: tpeat@purdue.edu.
Snehal M GaikwadLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Wendy DuboisLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Nana Gyabaah-KessieLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Shuling ZhangLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Sayeh GorjifardLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; University of Washington, Seattle, WA, USA.
Zaw PhyoLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Johns Hopkins University, Baltimore, MD, USA.
Megan AndresLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Johns Hopkins University, Baltimore, MD, USA.
V Keith HughittLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
R Mark SimpsonLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Margaret A MillerDepartment of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
Andrew T GirvinPalantir Technologies, Palo Alto, CA, USA.
Andrew TaylorPalantir Technologies, Palo Alto, CA, USA.
Daniel WilliamsPalantir Technologies, Palo Alto, CA, USA.
Nelson D'AntonioPalantir Technologies, Palo Alto, CA, USA.
Yong ZhangLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Office of Oncologic Diseases, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD, USA.
Adhithi RajagopalanMcArdle Research Labs, University of Wisconsin, Madison, WI, USA.
Evan FlietnerMcArdle Research Labs, University of Wisconsin, Madison, WI, USA.
Kelli WilsonChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Xiaohu ZhangChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Paul ShinnChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Carleen Klumpp-ThomasChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Crystal McKnightChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Zina ItkinChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Lu ChenChemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Dickran KazandijianLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, USA.
Jing ZhangMcArdle Research Labs, University of Wisconsin, Madison, WI, USA.
Aleksandra M MichalowskiLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
John K SimmonsNatera, San Carlos, CA, USA.
Jonathan KeatsTranslational Genomics Research Institute, Phoenix, AZ, USA.
Craig J ThomasLymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA; Chemical Genomics Center, Division of Preclinical Innovation, National Center for Advancing Translational Sciences, Bethesda, MD, USA.
Beverly A MockLaboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA. Electronic address: mockb@mail.nih.gov.
National Cancer Institute · USNational Center for Advancing Translational Sciences · USUniversity of Wisconsin–Madison · USJohns Hopkins University · USPurdue University West Lafayette · USNatera (United States) · USSylvester Comprehensive Cancer Center · USTranslational Genomics Research Institute · USUnited States Food and Drug Administration · USUniversity of Washington · US

Funding

Research Services Section (RSS)ZICTR000242 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI WILSON, KELLI · 2015 to 2025
$64.9M
Molecular Pathology Research for Cancer Diagnostics and BiomarkersZICBC010953 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SIMPSON, ROBERT · 2009 to 2025
$22.9M
Comparative Biomedical Scientist Training ProgramZIGBC010931 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI SIMPSON, ROBERT · 2009 to 2025
$20.0M
Preclinical Testing of HDAC, mTOR and MYC InhibitorsZIABC011065 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MOCK, BEVERLY · 2009 to 2025
$10.6M
HTS enabled examination of drug combinationsZIATR000047 · NCATS · NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES · PI THOMAS, CRAIG · 2015 to 2025
$7.1M
The role of TCOF1 in germline predisposition to and in leukemic transformation of chronic myelomonocytic leukemiaR01CA152108 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Jing Zhang · 2011 to 2026
$5.4M
Intramural NIH HHS ZIA BC011065NCI NIH HHS R01 CA152108
6 · The paper itself

Abstract

Drug resistance and disease progression are common in multiple myeloma (MM) patients, underscoring the need for new therapeutic combinations. A high-throughput drug screen in 47 MM cell lines and in silico Huber robust regression analysis of drug responses revealed 43 potentially synergistic combinations. We hypothesized that effective combinations would reduce MYC expression and enhance p16 activity. Six combinations cooperatively reduced MYC protein, frequently over-expressed in MM and also cooperatively increased p16 expression, frequently downregulated in MM. Synergistic reductions in viability were observed with top combinations in proteasome inhibitor-resistant and sensitive MM cell lines, while sparing fibroblasts. Three combinations significantly prolonged survival in a transplantable Ras-driven allograft model of advanced MM closely recapitulating high-risk/refractory myeloma in humans and reduced viability of ex vivo treated patient cells. Common genetic pathways similarly downregulated by these combinations promoted cell cycle transition, whereas pathways most upregulated were involved in TGFβ/SMAD signaling. These preclinical data identify potentially useful drug combinations for evaluation in drug-resistant MM and reveal potential mechanisms of combined drug sensitivity.

Indexed as

Multiple MyelomaCell CycleCell Line, TumorDrug CombinationsDrug Resistance, NeoplasmDrug SynergismHigh-Throughput Screening AssaysHumansDrug CombinationsDinaciclibEntinostatMYCMyelomap16

Identifiers

PMID37356470
PMCPMC10408729
OpenAlexW4381893760

What OpenQuestion holds

Textmetadata
LicenceTDM
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.