Evidence map›Paper›PMID 32243838›Full record

ArticleCancer cell2020

A Deregulated HOX Gene Axis Confers an Epigenetic Vulnerability in KRAS-Mutant Lung Cancers.

Stephanie L Guerra, Ophélia Maertens, Ryan Kuzmickas, Thomas De Raedt, Richard O Adeyemi, Caroline J Guild, Shawna Guillemette, Amanda J Redig, Emily S Chambers, Man Xu and 5 more

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

Article in Cancer cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 55 citations in OpenAlex.

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  12. Modern therapies of nonsmall cell lung cancer.Journal of applied genetics · 2023
    Review
  13. MDiscover oncology · 2023
    Article
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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

15 authors at 3 institutions in 1 country.

Stephanie L GuerraGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Ophélia MaertensGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Ryan KuzmickasGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Thomas De RaedtGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Richard O AdeyemiGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Caroline J GuildGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Shawna GuillemetteGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
Amanda J RedigLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Emily S ChambersLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Man XuBelfer Center for Applied Cancer Science, Boston, MA 02115, USA.
Hong TivExperimental Therapeutic Core, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Sandro SantagataHarvard Medical School, Boston, MA 02115, USA; Departments of Pathology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA.
Pasi A JänneHarvard Medical School, Boston, MA 02115, USA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Belfer Center for Applied Cancer Science, Boston, MA 02115, USA.
Stephen J ElledgeGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Karen CichowskiGenetics Division, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA; Ludwig Center at Harvard, Harvard Medical School, Boston, MA 02115, USA. Electronic address: kcichowski@rics.bwh.harvard.edu.
Brigham and Women's Hospital · USDana-Farber Cancer Institute · USHarvard University · US

Funding

Elucidating the Regulation and Function of the NF1 tumor suppressorR01CA111754 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI KAREN M CICHOWSKI · 2005 to 2026
$7.4M
NCI NIH HHS R01 CA111754
6 · The paper itself

Abstract

While KRAS mutations are common in non-small cell lung cancer (NSCLC), effective treatments are lacking. Here, we report that half of KRAS-mutant NSCLCs aberrantly express the homeobox protein HOXC10, largely due to unappreciated defects in PRC2, which confers sensitivity to combined BET/MEK inhibitors in xenograft and PDX models. Efficacy of the combination is dependent on suppression of HOXC10 by BET inhibitors. We further show that HOXC10 regulates the expression of pre-replication complex (pre-RC) proteins in sensitive tumors. Accordingly, BET/MEK inhibitors suppress pre-RC proteins in cycling cells, triggering stalled replication, DNA damage, and death. These studies reveal a promising therapeutic strategy for KRAS-mutant NSCLCs, identify a predictive biomarker of response, and define a subset of NSCLCs with a targetable epigenetic vulnerability.

Indexed as

Epigenesis, GeneticMutationAcrylonitrileAniline CompoundsAnimalsApoptosisBiomarkers, TumorBromodomain Containing ProteinsCarcinoma, Non-Small-Cell LungCell ProliferationFemaleGene Expression Regulation, NeoplasticHomeodomain ProteinsHumansLung NeoplasmsMaleAcrylonitrileAniline CompoundsBiomarkers, Tumorbromodomain and extra-terminal domain protein, humanBromodomain Containing ProteinsHomeodomain ProteinsHOXC10 protein, humanKRAS protein, humanMAP Kinase Kinase 1MEK inhibitor IProtein Kinase InhibitorsProteinsProto-Oncogene Proteins p21(ras)BETcombination therapyEEDHOXC10KRASlung cancerMEKNSCLCPRC2SUZ12

Identifiers

PMID32243838
PMCPMC10805385
OpenAlexW3014162795

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.