{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/4448"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/4448","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"The Emergence of Diverse Drug-Resistance Mechanisms from Drug Tolerant Cancer Persister Cells","abstract":"Cancer therapy has traditionally focused on eliminating fast-growing populations of cells, yet a growing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a slow-growing "persister" state. 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 and clinical relevance of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here, we compared persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We found, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies had 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--from which drug-resistance heterogeneity can emerge.","abstract_html":"Cancer therapy has traditionally focused on eliminating fast-growing populations of cells, yet a growing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a slow-growing "persister" state. 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 and clinical relevance of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here, we compared persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We found, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies had 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--from which drug-resistance heterogeneity can emerge.","abstract_has_math":false,"creators":["Ramirez, Michael Edward"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Mendell, Joshua T.","Shay, Jerry W.","Cobb, Melanie H.","Altschuler, Steven J.","Wu, Lani","Wu, Jiang I."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-01-04T21:09:49Z","date_published":"2018-01-04T21:09:49Z","updated_at":"2026-07-24T05:52:15Z","subjects":["Antineoplastic Agents","Drug Resistance, Neoplasm","Erlotinib Hydrochloride","Lung Neoplasms"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1017760182"],"render_values":[{"text":"1017760182","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/4448","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Mendell, Joshua T.","Shay, Jerry W.","Cobb, Melanie H.","Altschuler, Steven J.","Wu, Lani","Wu, Jiang I."]},{"key":"dc:creator","label":"Author","values":["Ramirez, Michael Edward"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-01-04T21:09:49Z","2015-12","2015-08-31","December 2015","2018-01-04T21:03:43Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Antineoplastic Agents","Drug Resistance, Neoplasm","Erlotinib Hydrochloride","Lung Neoplasms"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/4448","1017760182"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Cancer therapy has traditionally focused on eliminating fast-growing populations of cells, yet a growing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a slow-growing "persister" state. 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 and clinical relevance of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here, we compared persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We found, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies had 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--from which drug-resistance heterogeneity can emerge."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["The Emergence of Diverse Drug-Resistance Mechanisms from Drug Tolerant Cancer Persister Cells"]}]}],"canonical_facts":{"dc:contributor":["Mendell, Joshua T.","Shay, Jerry W.","Cobb, Melanie H.","Altschuler, Steven J.","Wu, Lani","Wu, Jiang I."],"dc:creator":["Ramirez, Michael Edward"],"dc:date":["2018-01-04T21:09:49Z","2015-12","2015-08-31","December 2015","2018-01-04T21:03:43Z"],"dc:description":["Cancer therapy has traditionally focused on eliminating fast-growing populations of cells, yet a growing body of evidence suggests that small subpopulations of cancer cells can evade strong selective drug pressure by entering a slow-growing "persister" state. 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 and clinical relevance of drug-resistance mechanisms that can expand from a persister bottleneck is unknown. Here, we compared persister-derived, erlotinib-resistant colonies that arose from a single, EGFR-addicted lung cancer cell. We found, using a combination of large-scale drug screening and whole-exome sequencing, that our erlotinib-resistant colonies had 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--from which drug-resistance heterogeneity can emerge."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/4448","1017760182"],"dc:language":["en"],"dc:subject":["Antineoplastic Agents","Drug Resistance, Neoplasm","Erlotinib Hydrochloride","Lung Neoplasms"],"dc:title":["The Emergence of Diverse Drug-Resistance Mechanisms from Drug Tolerant Cancer Persister Cells"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:15Z"}