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Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance

Author

Listed:
  • Sydney M. Shaffer

    (University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Margaret C. Dunagin

    (University of Pennsylvania)

  • Stefan R. Torborg

    (University of Pennsylvania
    University of Pennsylvania)

  • Eduardo A. Torre

    (University of Pennsylvania
    Perelman School of Medicine, University of Pennsylvania)

  • Benjamin Emert

    (Perelman School of Medicine, University of Pennsylvania
    Genomics and Computational Biology Group, University of Pennsylvania)

  • Clemens Krepler

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Marilda Beqiri

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Katrin Sproesser

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Patricia A. Brafford

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Min Xiao

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Elliott Eggan

    (Perelman School of Medicine, University of Pennsylvania)

  • Ioannis N. Anastopoulos

    (Perelman School of Medicine, University of Pennsylvania)

  • Cesar A. Vargas-Garcia

    (Electrical and Computer Engineering, University of Delaware)

  • Abhyudai Singh

    (Electrical and Computer Engineering, University of Delaware
    Biomedical Engineering, University of Delaware)

  • Katherine L. Nathanson

    (Perelman School of Medicine, University of Pennsylvania)

  • Meenhard Herlyn

    (The Wistar Institute, Molecular and Cellular Oncogenesis Program, Melanoma Research Center)

  • Arjun Raj

    (University of Pennsylvania
    University of Pennsylvania)

Abstract

Through drug exposure, a rare, transient transcriptional program characterized by high levels of expression of known resistance drivers can get ‘burned in’, leading to the selection of cells endowed with a transcriptional drug resistance and thus more chemoresistant cancers.

Suggested Citation

  • Sydney M. Shaffer & Margaret C. Dunagin & Stefan R. Torborg & Eduardo A. Torre & Benjamin Emert & Clemens Krepler & Marilda Beqiri & Katrin Sproesser & Patricia A. Brafford & Min Xiao & Elliott Eggan , 2017. "Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance," Nature, Nature, vol. 546(7658), pages 431-435, June.
    • Handle: RePEc:nat:nature:v:546:y:2017:i:7658:d:10.1038_nature22794
    DOI: 10.1038/nature22794
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    Cited by:

    1. Guillaume Harmange & Raúl A. Reyes Hueros & Dylan L. Schaff & Benjamin Emert & Michael Saint-Antoine & Laura C. Kim & Zijian Niu & Shivani Nellore & Mitchell E. Fane & Gretchen M. Alicea & Ashani T. W, 2023. "Disrupting cellular memory to overcome drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. G. Gambardella & G. Viscido & B. Tumaini & A. Isacchi & R. Bosotti & D. di Bernardo, 2022. "A single-cell analysis of breast cancer cell lines to study tumour heterogeneity and drug response," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    3. Xinrui Zhou & Wan Yi Seow & Norbert Ha & Teh How Cheng & Lingfan Jiang & Jeeranan Boonruangkan & Jolene Jie Lin Goh & Shyam Prabhakar & Nigel Chou & Kok Hao Chen, 2024. "Highly sensitive spatial transcriptomics using FISHnCHIPs of multiple co-expressed genes," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Jessica A Lee & Siavash Riazi & Shahla Nemati & Jannell V Bazurto & Andreas E Vasdekis & Benjamin J Ridenhour & Christopher H Remien & Christopher J Marx, 2019. "Microbial phenotypic heterogeneity in response to a metabolic toxin: Continuous, dynamically shifting distribution of formaldehyde tolerance in Methylobacterium extorquens populations," PLOS Genetics, Public Library of Science, vol. 15(11), pages 1-38, November.
    5. Jonathan Liu & Donald Hansen & Elizabeth Eck & Yang Joon Kim & Meghan Turner & Simon Alamos & Hernan Garcia, 2021. "Real-time single-cell characterization of the eukaryotic transcription cycle reveals correlations between RNA initiation, elongation, and cleavage," PLOS Computational Biology, Public Library of Science, vol. 17(5), pages 1-26, May.
    6. Jun Dai & Shuyu Zheng & Matías M. Falco & Jie Bao & Johanna Eriksson & Sanna Pikkusaari & Sofia Forstén & Jing Jiang & Wenyu Wang & Luping Gao & Fernando Perez-Villatoro & Olli Dufva & Khalid Saeed & , 2024. "Tracing back primed resistance in cancer via sister cells," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Anastasia Samarkina & Markus Kirolos Youssef & Paola Ostano & Soumitra Ghosh & Min Ma & Beatrice Tassone & Tatiana Proust & Giovanna Chiorino & Mitchell P. Levesque & Sandro Goruppi & Gian Paolo Dotto, 2023. "Androgen receptor is a determinant of melanoma targeted drug resistance," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    8. Anissa El Marrahi & Fabio Lipreri & Ziqi Kang & Louise Gsell & Alper Eroglu & David Alber & Jean Hausser, 2023. "NIPMAP: niche-phenotype mapping of multiplex histology data by community ecology," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    9. Franziska Haderk & Yu-Ting Chou & Lauren Cech & Celia Fernández-Méndez & Johnny Yu & Victor Olivas & Ismail M. Meraz & Dora Barbosa Rabago & D. Lucas Kerr & Carlos Gomez & David V. Allegakoen & Juan G, 2024. "Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Jean-Baptiste Lugagne & Caroline M. Blassick & Mary J. Dunlop, 2024. "Deep model predictive control of gene expression in thousands of single cells," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    11. Singh, Abhyudai & Vahdat, Zahra & Xu, Zikai, 2019. "Time-triggered stochastic hybrid systems with two timer-dependent resets," OSF Preprints u8fzg, Center for Open Science.
    12. Jaishree Tripathi & Lei Zhu & Sourav Nayak & Michal Stoklasa & Zbynek Bozdech, 2022. "Stochastic expression of invasion genes in Plasmodium falciparum schizonts," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Xue Zhang & Shishir M. Pant & Cecily C. Ritch & Hsin-Yao Tang & Hongguang Shao & Harsh Dweep & Yao-Yu Gong & Rebekah Brooks & Patricia Brafford & Adam J. Wolpaw & Yool Lee & Ashani Weeraratna & Amita , 2024. "Cell state dependent effects of Bmal1 on melanoma immunity and tumorigenicity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    14. Heike Chauvistré & Batool Shannan & Sheena M. Daignault-Mill & Robert J. Ju & Daniel Picard & Stefanie Egetemaier & Renáta Váraljai & Christine S. Gibhardt & Antonio Sechi & Farnusch Kaschani & Oliver, 2022. "Persister state-directed transitioning and vulnerability in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Claudia Capparelli & Timothy J. Purwin & McKenna Glasheen & Signe Caksa & Manoela Tiago & Nicole Wilski & Danielle Pomante & Sheera Rosenbaum & Mai Q. Nguyen & Weijia Cai & Janusz Franco-Barraza & Ric, 2022. "Targeting SOX10-deficient cells to reduce the dormant-invasive phenotype state in melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    16. Yelyzaveta Shlyakhtina & Bianca Bloechl & Maximiliano M. Portal, 2023. "BdLT-Seq as a barcode decay-based method to unravel lineage-linked transcriptome plasticity," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    17. Caitlin E. Mills & Kartik Subramanian & Marc Hafner & Mario Niepel & Luca Gerosa & Mirra Chung & Chiara Victor & Benjamin Gaudio & Clarence Yapp & Ajit J. Nirmal & Nicholas Clark & Peter K. Sorger, 2022. "Multiplexed and reproducible high content screening of live and fixed cells using Dye Drop," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

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