{"id":"https://openalex.org/W2514967531","doi":"https://doi.org/10.1371/journal.pcbi.1005077","title":"Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors","display_name":"Leveraging Hypoxia-Activated Prodrugs to Prevent Drug Resistance in Solid Tumors","publication_year":2016,"publication_date":"2016-08-25","ids":{"openalex":"https://openalex.org/W2514967531","doi":"https://doi.org/10.1371/journal.pcbi.1005077","mag":"2514967531","pmid":"https://pubmed.ncbi.nlm.nih.gov/27560187"},"language":"en","primary_location":{"id":"doi:10.1371/journal.pcbi.1005077","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1005077","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005077&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005077&type=printable","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5084996695","display_name":"Danika Lindsay","orcid":null},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Danika Lindsay","raw_affiliation_strings":["School of Mathematics, University of Minnesota, Minneapolis, Minnesota, United States of America"],"affiliations":[{"raw_affiliation_string":"School of Mathematics, University of Minnesota, Minneapolis, Minnesota, United States of America","institution_ids":["https://openalex.org/I130238516"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046571063","display_name":"Colleen M. Garvey","orcid":null},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Colleen M. Garvey","raw_affiliation_strings":["Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, United States of America"],"affiliations":[{"raw_affiliation_string":"Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, United States of America","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079254926","display_name":"Shannon M. Mumenthaler","orcid":"https://orcid.org/0000-0003-2687-3769"},"institutions":[{"id":"https://openalex.org/I1174212","display_name":"University of Southern California","ror":"https://ror.org/03taz7m60","country_code":"US","type":"education","lineage":["https://openalex.org/I1174212"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Shannon M. Mumenthaler","raw_affiliation_strings":["Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, United States of America"],"affiliations":[{"raw_affiliation_string":"Lawrence J. Ellison Institute for Transformative Medicine, University of Southern California, Los Angeles, California, United States of America","institution_ids":["https://openalex.org/I1174212"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5035234146","display_name":"Jasmine Foo","orcid":"https://orcid.org/0000-0001-8238-325X"},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Jasmine Foo","raw_affiliation_strings":["School of Mathematics, University of Minnesota, Minneapolis, Minnesota, United States of America"],"affiliations":[{"raw_affiliation_string":"School of Mathematics, University of Minnesota, Minneapolis, Minnesota, United States of America","institution_ids":["https://openalex.org/I130238516"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":["https://openalex.org/A5035234146","https://openalex.org/A5079254926"],"corresponding_institution_ids":["https://openalex.org/I1174212","https://openalex.org/I130238516"],"apc_list":{"value":2655,"currency":"USD","value_usd":2655},"apc_paid":{"value":2655,"currency":"USD","value_usd":2655},"fwci":0.9172,"has_fulltext":true,"cited_by_count":24,"citation_normalized_percentile":{"value":0.73927865,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":98},"biblio":{"volume":"12","issue":"8","first_page":"e1005077","last_page":"e1005077"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.9991999864578247,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.9991999864578247,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.9991000294685364,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":0.9987000226974487,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/prodrug","display_name":"Prodrug","score":0.7702031135559082},{"id":"https://openalex.org/keywords/erlotinib","display_name":"Erlotinib","score":0.6765378713607788},{"id":"https://openalex.org/keywords/drug","display_name":"Drug","score":0.6478767395019531},{"id":"https://openalex.org/keywords/context","display_name":"Context (archaeology)","score":0.48751088976860046},{"id":"https://openalex.org/keywords/hypoxia","display_name":"Hypoxia (environmental)","score":0.4625413417816162},{"id":"https://openalex.org/keywords/pharmacology","display_name":"Pharmacology","score":0.44227632880210876},{"id":"https://openalex.org/keywords/tumor-hypoxia","display_name":"Tumor hypoxia","score":0.4260135293006897},{"id":"https://openalex.org/keywords/tirapazamine","display_name":"Tirapazamine","score":0.42254188656806946},{"id":"https://openalex.org/keywords/combination-therapy","display_name":"Combination therapy","score":0.4186648726463318},{"id":"https://openalex.org/keywords/medicine","display_name":"Medicine","score":0.4032464623451233},{"id":"https://openalex.org/keywords/cancer-research","display_name":"Cancer research","score":0.37657612562179565},{"id":"https://openalex.org/keywords/cancer","display_name":"Cancer","score":0.27823859453201294},{"id":"https://openalex.org/keywords/radiation-therapy","display_name":"Radiation therapy","score":0.2761760950088501},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.23259907960891724},{"id":"https://openalex.org/keywords/chemistry","display_name":"Chemistry","score":0.1931760311126709},{"id":"https://openalex.org/keywords/internal-medicine","display_name":"Internal medicine","score":0.15023252367973328},{"id":"https://openalex.org/keywords/cytotoxicity","display_name":"Cytotoxicity","score":0.11872032284736633},{"id":"https://openalex.org/keywords/epidermal-growth-factor-receptor","display_name":"Epidermal growth factor receptor","score":0.11016926169395447},{"id":"https://openalex.org/keywords/in-vitro","display_name":"In vitro","score":0.0975290834903717}],"concepts":[{"id":"https://openalex.org/C108215921","wikidata":"https://www.wikidata.org/wiki/Q603741","display_name":"Prodrug","level":2,"score":0.7702031135559082},{"id":"https://openalex.org/C2778087573","wikidata":"https://www.wikidata.org/wiki/Q418369","display_name":"Erlotinib","level":4,"score":0.6765378713607788},{"id":"https://openalex.org/C2780035454","wikidata":"https://www.wikidata.org/wiki/Q8386","display_name":"Drug","level":2,"score":0.6478767395019531},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.48751088976860046},{"id":"https://openalex.org/C7836513","wikidata":"https://www.wikidata.org/wiki/Q1641506","display_name":"Hypoxia (environmental)","level":3,"score":0.4625413417816162},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.44227632880210876},{"id":"https://openalex.org/C2779081379","wikidata":"https://www.wikidata.org/wiki/Q7852677","display_name":"Tumor hypoxia","level":3,"score":0.4260135293006897},{"id":"https://openalex.org/C2776313096","wikidata":"https://www.wikidata.org/wiki/Q3529346","display_name":"Tirapazamine","level":4,"score":0.42254188656806946},{"id":"https://openalex.org/C2776999253","wikidata":"https://www.wikidata.org/wiki/Q1304270","display_name":"Combination therapy","level":2,"score":0.4186648726463318},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4032464623451233},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.37657612562179565},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.27823859453201294},{"id":"https://openalex.org/C509974204","wikidata":"https://www.wikidata.org/wiki/Q180507","display_name":"Radiation therapy","level":2,"score":0.2761760950088501},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.23259907960891724},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.1931760311126709},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.15023252367973328},{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.11872032284736633},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.11016926169395447},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.0975290834903717},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.0},{"id":"https://openalex.org/C151730666","wikidata":"https://www.wikidata.org/wiki/Q7205","display_name":"Paleontology","level":1,"score":0.0},{"id":"https://openalex.org/C540031477","wikidata":"https://www.wikidata.org/wiki/Q629","display_name":"Oxygen","level":2,"score":0.0},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.0}],"mesh":[{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D000069347","descriptor_name":"Erlotinib Hydrochloride","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D000860","descriptor_name":"Hypoxia","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000860","descriptor_name":"Hypoxia","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000860","descriptor_name":"Hypoxia","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D002289","descriptor_name":"Carcinoma, Non-Small-Cell Lung","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D002289","descriptor_name":"Carcinoma, Non-Small-Cell Lung","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D002289","descriptor_name":"Carcinoma, Non-Small-Cell Lung","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D008175","descriptor_name":"Lung Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D011355","descriptor_name":"Prodrugs","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D019008","descriptor_name":"Drug Resistance, Neoplasm","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D019295","descriptor_name":"Computational Biology","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1371/journal.pcbi.1005077","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1005077","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005077&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},{"id":"pmid:27560187","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/27560187","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLoS computational biology","raw_type":null},{"id":"pmh:oai:doaj.org/article:ef50b8c52ca3440e80a214f80408d638","is_oa":true,"landing_page_url":"https://doaj.org/article/ef50b8c52ca3440e80a214f80408d638","pdf_url":null,"source":{"id":"https://openalex.org/S112646816","display_name":"SHILAP Revista de lepidopterolog\u00eda","issn_l":"0300-5267","issn":["0300-5267","2340-4078"],"is_oa":true,"is_in_doaj":true,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"PLoS Computational Biology, Vol 12, Iss 8, p e1005077 (2016)","raw_type":"article"},{"id":"pmh:oai:europepmc.org:3977973","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4999195","pdf_url":null,"source":{"id":"https://openalex.org/S4306400806","display_name":"Europe PMC (PubMed Central)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":"https://openalex.org/I1303153112","host_organization_name":"European Bioinformatics Institute","host_organization_lineage":["https://openalex.org/I1303153112"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1371/journal.pcbi.1005077","is_oa":true,"landing_page_url":"https://doi.org/10.1371/journal.pcbi.1005077","pdf_url":"https://journals.plos.org/ploscompbiol/article/file?id=10.1371/journal.pcbi.1005077&type=printable","source":{"id":"https://openalex.org/S86033158","display_name":"PLoS Computational Biology","issn_l":"1553-734X","issn":["1553-734X","1553-7358"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310315706","host_organization_name":"Public Library of Science","host_organization_lineage":["https://openalex.org/P4310315706"],"host_organization_lineage_names":["Public Library of Science"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"PLOS Computational Biology","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.7599999904632568,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"awards":[{"id":"https://openalex.org/G1680491773","display_name":null,"funder_award_id":"DMS-1349724","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G2268000618","display_name":null,"funder_award_id":"00039202","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G2516804138","display_name":"Understanding stochasticity in cancer recurrence timing","funder_award_id":"1224362","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G2702435604","display_name":null,"funder_award_id":"13497","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G3924427782","display_name":"CAREER: Stochastic Models of Cancer Evolution","funder_award_id":"1349724","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G493693001","display_name":null,"funder_award_id":"0039202","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G5680455586","display_name":null,"funder_award_id":"U54CA143907","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G5950577451","display_name":null,"funder_award_id":"NIH U54","funder_id":"https://openalex.org/F4320332161","funder_display_name":"National Institutes of Health"},{"id":"https://openalex.org/G6429368441","display_name":"Quantitative Analysis of the Semicircular Canals of Fossil Primates: A Test of Hypotheses About Locomotion in Extinct Species","funder_award_id":"0003920","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G7166585143","display_name":null,"funder_award_id":"00039202","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G750410376","display_name":null,"funder_award_id":"DMS-1224362","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"},{"id":"https://openalex.org/G7677597897","display_name":null,"funder_award_id":"39202","funder_id":"https://openalex.org/F4320306076","funder_display_name":"National Science Foundation"}],"funders":[{"id":"https://openalex.org/F4320306076","display_name":"National Science Foundation","ror":"https://ror.org/021nxhr62"},{"id":"https://openalex.org/F4320332161","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W2514967531.pdf","grobid_xml":"https://content.openalex.org/works/W2514967531.grobid-xml"},"referenced_works_count":49,"referenced_works":["https://openalex.org/W1223908403","https://openalex.org/W1509720837","https://openalex.org/W1561977930","https://openalex.org/W1977785806","https://openalex.org/W1991880013","https://openalex.org/W2002937040","https://openalex.org/W2020281792","https://openalex.org/W2020299413","https://openalex.org/W2025521327","https://openalex.org/W2030227571","https://openalex.org/W2034072253","https://openalex.org/W2041997066","https://openalex.org/W2049484790","https://openalex.org/W2051990692","https://openalex.org/W2057895959","https://openalex.org/W2059905849","https://openalex.org/W2065141010","https://openalex.org/W2066128027","https://openalex.org/W2078075009","https://openalex.org/W2079142824","https://openalex.org/W2080000401","https://openalex.org/W2083841434","https://openalex.org/W2091940240","https://openalex.org/W2093424637","https://openalex.org/W2104928951","https://openalex.org/W2115078677","https://openalex.org/W2121944811","https://openalex.org/W2122995470","https://openalex.org/W2123431502","https://openalex.org/W2125257427","https://openalex.org/W2126669622","https://openalex.org/W2128560067","https://openalex.org/W2135836172","https://openalex.org/W2136849860","https://openalex.org/W2139236349","https://openalex.org/W2141635226","https://openalex.org/W2142865455","https://openalex.org/W2145980885","https://openalex.org/W2155582899","https://openalex.org/W2161959587","https://openalex.org/W2164417230","https://openalex.org/W2165836181","https://openalex.org/W2171412952","https://openalex.org/W2181858460","https://openalex.org/W2206903933","https://openalex.org/W2255357451","https://openalex.org/W2270297461","https://openalex.org/W2332701617","https://openalex.org/W4301258661"],"related_works":["https://openalex.org/W2914293180","https://openalex.org/W3203002242","https://openalex.org/W2933531144","https://openalex.org/W4224142852","https://openalex.org/W2586840087","https://openalex.org/W4280615613","https://openalex.org/W2089349861","https://openalex.org/W4310938584","https://openalex.org/W4248259211","https://openalex.org/W2102907645"],"abstract_inverted_index":{"Experimental":[0],"studies":[1],"have":[2,70],"shown":[3,72],"that":[4,83,100,194,202],"one":[5],"key":[6],"factor":[7],"in":[8,15,64,76,128,236,259,279],"driving":[9],"the":[10,24,84,95,129,143,184,245,280],"emergence":[11],"of":[12,26,49,59,78,86,132,164,186,225,238,247,261],"drug":[13,227],"resistance":[14,208],"solid":[16],"tumors":[17],"is":[18,139],"tumor":[19,51,120,198,231,262],"hypoxia,":[20],"which":[21,138],"leads":[22,228],"to":[23,44,46,106,117,160,189,196,229,275],"formation":[25],"localized":[27],"environmental":[28],"niches":[29],"where":[30],"drug-resistant":[31],"cell":[32,135],"populations":[33],"can":[34,103],"evolve":[35],"and":[36,52,99,157,179,233,241,253],"survive.":[37],"Hypoxia-activated":[38],"prodrugs":[39,90,271],"(HAPs)":[40],"are":[41,62],"compounds":[42],"designed":[43],"penetrate":[45],"hypoxic":[47],"regions":[48],"a":[50,73,150,162,168],"release":[53],"cytotoxic":[54],"or":[55,122,217],"cytostatic":[56],"agents;":[57],"several":[58,77],"these":[60,79,89,205],"HAPs":[61,113],"currently":[63],"clinical":[65,156],"trial.":[66],"However,":[67],"preliminary":[68],"results":[69,265],"not":[71],"survival":[74],"benefit":[75],"trials.":[80],"We":[81,124,148,173,200],"hypothesize":[82],"efficacy":[85],"treatments":[87],"involving":[88],"depends":[91],"heavily":[92],"on":[93],"identifying":[94],"correct":[96],"treatment":[97,165,181],"schedule,":[98],"mathematical":[101,152],"modeling":[102],"be":[104,273],"used":[105,274],"help":[107],"design":[108,174],"potential":[109],"therapeutic":[110,277],"strategies":[111,182,243],"combining":[112,167,204],"with":[114,142,171,214],"standard":[115],"therapies":[116,206],"achieve":[118],"long-term":[119],"control":[121],"eradication.":[123],"develop":[125,149],"this":[126],"framework":[127],"specific":[130,191],"context":[131],"EGFR-driven":[133],"non-small":[134],"lung":[136],"cancer,":[137],"commonly":[140],"treated":[141],"tyrosine":[144],"kinase":[145],"inhibitor":[146],"erlotinib.":[147,172],"stochastic":[151],"model,":[153],"parametrized":[154],"using":[155],"experimental":[158],"data,":[159],"explore":[161],"spectrum":[163],"regimens":[166],"HAP,":[169],"evofosfamide,":[170],"combination":[175,192],"toxicity":[176],"constraint":[177],"models":[178],"optimize":[180],"over":[183],"space":[185],"tolerated":[187],"schedules":[188,193],"identify":[190],"lead":[195],"optimal":[197],"control.":[199],"find":[201],"(i)":[203],"delays":[207],"longer":[209],"than":[210],"any":[211],"monotherapy":[212],"schedule":[213],"either":[215],"evofosfamide":[216,251],"erlotinib":[218,255],"alone,":[219],"(ii)":[220],"sequentially":[221],"alternating":[222],"single":[223],"doses":[224],"each":[226],"minimal":[230],"burden":[232],"maximal":[234],"reduction":[235,260],"probability":[237],"developing":[239],"resistance,":[240],"(iii)":[242],"minimizing":[244],"length":[246],"time":[248],"after":[249],"an":[250],"dose":[252],"before":[254],"confer":[256],"further":[257],"benefits":[258],"burden.":[263],"These":[264],"provide":[266],"insights":[267],"into":[268],"how":[269],"hypoxia-activated":[270],"may":[272],"enhance":[276],"effectiveness":[278],"clinic.":[281]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":4},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":3},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":1}],"updated_date":"2026-04-10T15:06:20.359241","created_date":"2025-10-10T00:00:00"}
