Evidence map›Paper›PMID 33417860›Full record

ArticleCell2021

Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy.

Sumaiyah K Rehman, Jennifer Haynes, Evelyne Collignon, Kevin R Brown, Yadong Wang, Allison M L Nixon, Jeffrey P Bruce, Jeffrey A Wintersinger, Arvind Singh Mer, Edwyn B L Lo and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 300 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
300citing papers in PubMed, 2 pooled it
–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

300 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  6. Autophagy modulation in cancer.Nature reviews. Drug discovery · 2026
    Review
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240 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Sumaiyah K RehmanPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Jennifer HaynesPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Evelyne CollignonLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada.
Kevin R BrownDonnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada.
Yadong WangPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Allison M L NixonDepartment of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Jeffrey P BrucePrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Jeffrey A WintersingerDonnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada; Vector Institute, Toronto, ON M5G 1M1, Canada.
Arvind Singh MerPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Edwyn B L LoPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Cherry LeungPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Evelyne Lima-FernandesPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Nicholas M PedleyPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Fraser SoaresPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada.
Sophie McGibbonDepartment of Physics, University of Toronto, Toronto, ON M5S 1A7, Canada.
Housheng Hansen HePrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Aaron PolletLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada.
Trevor J PughOntario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada; Clinical Genomics Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.
Benjamin Haibe-KainsPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 1L7, Canada.
Quaid MorrisDonnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Computer Science, University of Toronto, Toronto, ON M5T 3A1, Canada; Vector Institute, Toronto, ON M5G 1M1, Canada; Computational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Miguel Ramalho-SantosLunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5T 3L9, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: mrsantos@lunenfeld.ca.
Sidhartha GoyalDepartment of Physics, University of Toronto, Toronto, ON M5S 1A7, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada. Electronic address: goyal@physics.utoronto.ca.
Jason MoffatDonnelly Centre, University of Toronto, Toronto, ON M5S 3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5S 3E1, Canada. Electronic address: j.moffat@utoronto.ca.
Catherine A O'BrienPrincess Margaret Cancer Center, University Health Network, Toronto, ON M5G 1L7, Canada; Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Surgery, University Health Network, Toronto, ON M5G 1L7, Canada. Electronic address: cobrien@uhnresearch.ca.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Therapeutic Targeting of Breast Cancer Tumor Initiating CellsR01CA148761 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PEROU, CHARLES M, ROSEN, JEFFREY MARK · 2010 to 2025
$6.5M
CIHR 420231CIHR FDN-148479CIHR MOP-142375NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA148761
6 · The paper itself

Abstract

Cancer cells enter a reversible drug-tolerant persister (DTP) state to evade death from chemotherapy and targeted agents. It is increasingly appreciated that DTPs are important drivers of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer models to identify and characterize DTPs in response to chemotherapy. Barcode analysis revealed no loss of clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fit a mathematical model where all cancer cells, and not a small subpopulation, possess an equipotent capacity to become DTPs. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides insight into how cancer cells use a developmentally conserved mechanism to drive the DTP state, pointing to novel therapeutic opportunities to target DTPs.

Indexed as

DiapauseDrug Resistance, NeoplasmAnimalsAntineoplastic AgentsAutophagyCell Line, TumorClone CellsColorectal NeoplasmsEmbryo, MammalianGene Expression ProfilingGene Expression Regulation, NeoplasticGenetic HeterogeneityHumansIrinotecanMiceMice, Inbred NODAntineoplastic AgentsIrinotecanautophagybarcodechemotherapycolorectal cancerdiapausedrug tolerant persistersequipotentMRDmTORslow-cycling

Identifiers

PMID33417860
PMCPMC8437243

What OpenQuestion holds

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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.