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We are analyzing https://www.nature.com/articles/ncomms10690.

Title:
Diverse drug-resistance mechanisms can emerge from drug-tolerant cancer persister cells | Nature Communications
Description:
Cancer therapy has traditionally focused on eliminating fast-growing populations of cells. Yet, an increasing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a ‘persister’ state of negligible growth. This drug-tolerant state has been hypothesized to be part of an initial strategy towards eventual acquisition of bona fide drug-resistance mechanisms. However, the diversity of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here we compare persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We find, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies acquired diverse resistance mechanisms, including the most commonly observed clinical resistance mechanisms. Thus, the drug-tolerant persister state does not limit—and may even provide a latent reservoir of cells for—the emergence of heterogeneous drug-resistance mechanisms. Cancer cells that survive initial drug treatment can persist in the presence of drugs. Here, the authors generate persister cells that are resistant to the EGFR tyrosine kinase inhibitor erlotinib and show by single cell analysis that multiple mechanism give rise to the drug-resistant persister state.
Website Age:
30 years and 10 months (reg. 1994-08-11).

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Custom-built

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🌆 Monumental Traffic: 20M - 50M visitors per month


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$521,200 per month
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Keywords {🔍}

drug, percs, pubmed, cells, fig, resistance, cancer, erlotinib, article, cell, perc, supplementary, mechanisms, google, scholar, media, cas, response, drugs, persister, central, state, data, genetic, egfr, nature, growth, sensitivity, line, lung, met, drugresistance, drugtolerant, plates, performed, curves, colonies, methods, figs, diverse, treatment, persisters, erlotinibfree, mutations, screen, mutation, inhibitors, analysis, single, multiple,

Topics {✒️}

nature portfolio privacy policy middle grey lines advertising nature 462 nature individual resistance solutions drug-resistance solutions libraries 0/ reprints persister-derived erlotinib-resistant colonies small-cell lung cancer biomek liquid-handling robot synonymous single-nucleotide variant accurate long-read alignment burrows-wheeler alignment tool large-scale drug screen17 reversing melanoma cross-resistance drug-resistant cancer populations resistance-conferring genetic mutations somatic single-nucleotide variants large-scale drug screening drug-tolerant persister state8 sequence read archive small-scale ‘bypass’ experiment transient sirna-mediated knockdown accession number srp068321 interrogate drug-resistance mechanisms diverse drug-resistance mechanisms nci oncology set eliminating fast-growing populations drug-tolerant persister state egf receptor/akt pathway heterogeneous drug-resistance mechanisms 150–200-bp insert library long-term drug holiday diverse drug library permissions drug-category-response score perc drug-resistance mechanisms multiple cell lines smoothed drug-response curves cancer cell populations converting cancer therapies single genetic/epigenetic state tyrosine kinase inhibitors epidermal growth factor eliminating fast-growing cells relative drug-response score varying drug-response scores

Questions {❓}

  • Second-generation irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs): a better mousetrap?
  • Would different initial cells, passing through the persister bottleneck, give rise to the same resistance landscape?

Schema {🗺️}

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               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:Green Center for Systems Biology, University of Texas Southwestern Medical Center
            address:
               name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Satwik Rajaram
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:Green Center for Systems Biology, University of Texas Southwestern Medical Center
            address:
               name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Robert J. Steininger
      affiliation:
            name:Green Center for Systems Biology, University of Texas Southwestern Medical Center
            address:
               name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Daria Osipchuk
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Maike A. Roth
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Leanna S. Morinishi
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Louise Evans
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Weiyue Ji
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Chien-Hsiang Hsu
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Kevin Thurley
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
      name:Shuguang Wei
      affiliation:
            name:University of Texas Southwestern Medical Center
            address:
               name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Anwu Zhou
      affiliation:
            name:University of Texas Southwestern Medical Center
            address:
               name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Prasad R. Koduru
      affiliation:
            name:University of Texas Southwestern Medical Center
            address:
               name:Department of Pathology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Bruce A. Posner
      affiliation:
            name:University of Texas Southwestern Medical Center
            address:
               name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      name:Lani F. Wu
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:Green Center for Systems Biology, University of Texas Southwestern Medical Center
            address:
               name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Steven J. Altschuler
      affiliation:
            name:University of California, San Francisco
            address:
               name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
               type:PostalAddress
            type:Organization
            name:Green Center for Systems Biology, University of Texas Southwestern Medical Center
            address:
               name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
      name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Pathology, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA
      name:Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, USA
      name:Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, USA

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