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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?

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      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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