Evidence map›Paper›PMID 33417832›Full record

ArticleCancer cell2021

An Embryonic Diapause-like Adaptation with Suppressed Myc Activity Enables Tumor Treatment Persistence.

Eugen Dhimolea, Ricardo de Matos Simoes, Dhvanir Kansara, Aziz Al'Khafaji, Juliette Bouyssou, Xiang Weng, Shruti Sharma, Joseline Raja, Pallavi Awate, Ryosuke Shirasaki and 21 more

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PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
176citing papers in PubMed, 2 pooled it
15.7field-weighted citation impact, top 1% 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

176 citing papers in PubMed, 2 syntheses or guidelines pooled it, 251 citations in OpenAlex.

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116 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

31 authors at 9 institutions in 1 country.

Eugen DhimoleaDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA. Electronic address: eugen_dhimolea@dfci.harvard.edu.
Ricardo de Matos SimoesDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Dhvanir KansaraDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Aziz Al'KhafajiBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Juliette BouyssouDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Xiang WengDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA.
Shruti SharmaDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA.
Joseline RajaDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA.
Pallavi AwateDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA.
Ryosuke ShirasakiDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Huihui TangDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Brian J GlassnerDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Zhiyi LiuDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Dong GaoHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jordan BryanBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Samantha BenderBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jennifer RothBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Michal SchefferDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA.
Rinath JeselsohnDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Nathanael S GrayDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Irene GeorgakoudiDepartment of Biomedical Engineering, Tufts University, Medford, MA, USA.
Francisca VazquezBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Aviad TsherniakBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Yu ChenHuman Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Alana WelmDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Cihangir DuyDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA; Cancer Signaling and Epigenetics Program, Institute for Cancer Research, Cancer Epigenetics Institute, Fox Chase Cancer Center, Philadelphia, PA, USA.
Ari MelnickDepartment of Medicine, Weill Cornell Medicine, New York, NY, USA.
Boris BartholdyAlbert Einstein College of Medicine, Bronx, NY 10461, USA.
Myles BrownDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Aedin C CulhaneDepartment of Data Sciences, Dana-Farber Cancer Institute & Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Constantine S MitsiadesDepartment of Medical Oncology, Dana-Farber Cancer Institute Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Ludwig Center at Harvard, Boston, MA, USA. Electronic address: constantine_mitsiades@dfci.harvard.edu.
Broad Institute · USDana-Farber Cancer Institute · USHarvard University · USMemorial Sloan Kettering Cancer Center · USTufts University · USAlbert Einstein College of Medicine · USCornell University · USFox Chase Cancer Center · USUniversity of Utah · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
ATP-Dependent Chromatin Remodeling in Human MalignancyR01CA163915 · NCI · STANFORD UNIVERSITY · PI Gerald R. Crabtree · 2012 to 2026
$5.4M
Orchestra: A high performance biomedical supercomputing collaborativeS10RR028832 · NCRR · HARVARD MEDICAL SCHOOL · PI DANUSER, GAUDENZ · 2010 to 2010
$3.7M
Understanding the role of an aberrant hepatic nuclear transcription circuit in prostate cancer tumorigenesis and castration resistanceR01CA208100 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI CHEN, YU · 2017 to 2021
$2.5M
HIJACKING CANCER DRIVERS TO ACTIVATE PROAPOPTOTIC GENES IN DLBCLR01CA276167 · NCI · STANFORD UNIVERSITY · PI Gerald R. Crabtree, NATHANAEL Schiander GRAY · 2023 to 2026
$2.2M
Development and Application of Selective Covalent Cdk7 InhibitorsR01CA179483 · NCI · DANA-FARBER CANCER INST · PI GRAY, NATHANAEL SCHIANDER, MITSIADES, CONSTANTINE S. · 2014 to 2016
$1.5M
Department of DefenseNCI NIH HHS P30 CA008748NCI NIH HHS R01 CA163915NCI NIH HHS R01 CA179483NCI NIH HHS R01 CA208100NCI NIH HHS R01 CA276167NCRR NIH HHS S10 RR028832
6 · The paper itself

Abstract

Treatment-persistent residual tumors impede curative cancer therapy. To understand this cancer cell state we generated models of treatment persistence that simulate the residual tumors. We observe that treatment-persistent tumor cells in organoids, xenografts, and cancer patients adopt a distinct and reversible transcriptional program resembling that of embryonic diapause, a dormant stage of suspended development triggered by stress and associated with suppressed Myc activity and overall biosynthesis. In cancer cells, depleting Myc or inhibiting Brd4, a Myc transcriptional co-activator, attenuates drug cytotoxicity through a dormant diapause-like adaptation with reduced apoptotic priming. Conversely, inducible Myc upregulation enhances acute chemotherapeutic activity. Maintaining residual cells in dormancy after chemotherapy by inhibiting Myc activity or interfering with the diapause-like adaptation by inhibiting cyclin-dependent kinase 9 represent potential therapeutic strategies against chemotherapy-persistent tumor cells. Our study demonstrates that cancer co-opts a mechanism similar to diapause with adaptive inactivation of Myc to persist during treatment.

Indexed as

Adaptation, PhysiologicalAnimalsAntineoplastic AgentsApoptosisCell LineCell Line, TumorCyclin-Dependent Kinase 9DiapauseEmbryo, MammalianFemaleHEK293 CellsHumansMCF-7 CellsMiceProto-Oncogene Proteins c-mycTranscription FactorsAntineoplastic AgentsCyclin-Dependent Kinase 9Proto-Oncogene Proteins c-mycTranscription Factorsadaptation to stressbreast cancercancerCDK9CRISPRdiapausedrug persistenceMYCprostate cancerresidual tumor

Identifiers

PMID33417832
PMCPMC8670073
OpenAlexW3120587938

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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.