{"id":"https://openalex.org/W4392689768","doi":"https://doi.org/10.1158/1535-7163.c.6543498","title":"Data from Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors","display_name":"Data from Resistance Profile and Structural Modeling of Next-Generation ROS1 Tyrosine Kinase Inhibitors","publication_year":2023,"publication_date":"2023-04-03","ids":{"openalex":"https://openalex.org/W4392689768","doi":"https://doi.org/10.1158/1535-7163.c.6543498"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.c.6543498","doi":"https://doi.org/10.1158/1535-7163.c.6543498","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543498","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/1535-7163.c.6543498","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5001144101","display_name":"Clare Keddy","orcid":"https://orcid.org/0000-0001-5083-7296","observed_orcids":["https://orcid.org/0000-0001-5083-7296"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Clare Keddy","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5068120088","display_name":"Pushkar Shinde","orcid":"https://orcid.org/0000-0002-8086-4321","observed_orcids":["https://orcid.org/0000-0002-8086-4321"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Pushkar Shinde","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5064468392","display_name":"Kristen L. Jones","orcid":"https://orcid.org/0000-0002-8688-6679","observed_orcids":["https://orcid.org/0000-0002-8688-6679"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Kristen Jones","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103222030","display_name":"Stefanie Kaech","orcid":"https://orcid.org/0000-0002-6246-6434","observed_orcids":["https://orcid.org/0000-0002-6246-6434"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Stefanie Kaech","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5030479930","display_name":"Romel Somwar","orcid":"https://orcid.org/0000-0002-5282-6889","observed_orcids":["https://orcid.org/0000-0002-5282-6889"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Romel Somwar","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066661471","display_name":"Ujwal P. Shinde","orcid":"https://orcid.org/0000-0001-6229-2609","observed_orcids":["https://orcid.org/0000-0001-6229-2609"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ujwal Shinde","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5045185741","display_name":"Monika Ashok Davare","orcid":"https://orcid.org/0000-0003-1802-7597","observed_orcids":["https://orcid.org/0000-0003-1802-7597"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Monika A. Davare","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":1.0,"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"}},"topics":[{"id":"https://openalex.org/T10417","display_name":"Lung Cancer Treatments and Mutations","score":1.0,"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"}},{"id":"https://openalex.org/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.0,"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/T13779","display_name":"Cancer Mechanisms and Therapy","score":0.0,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/ros1-rearrangement","display_name":"ROS1 rearrangement","score":0.7269999980926514},{"id":"https://openalex.org/keywords/tyrosine-kinase-inhibitors","display_name":"tyrosine kinase inhibitors","score":0.953000009059906},{"id":"https://openalex.org/keywords/acquired-drug-resistance","display_name":"acquired drug resistance","score":0.8169999718666077},{"id":"https://openalex.org/keywords/entrectinib","display_name":"entrectinib","score":0.9700000286102295},{"id":"https://openalex.org/keywords/lorlatinib","display_name":"lorlatinib","score":0.9990000128746033},{"id":"https://openalex.org/keywords/repotrectinib","display_name":"repotrectinib","score":1.0},{"id":"https://openalex.org/keywords/crizotinib-resistance","display_name":"crizotinib resistance","score":0.7910000085830688},{"id":"https://openalex.org/keywords/macrocyclic-inhibitors","display_name":"macrocyclic inhibitors","score":0.7049999833106995},{"id":"https://openalex.org/keywords/cabozantinib","display_name":"cabozantinib","score":0.8029999732971191},{"id":"https://openalex.org/keywords/non-small-cell-lung-cancer","display_name":"non-small cell lung cancer","score":0.7960000038146973},{"id":"https://openalex.org/keywords/kinase-domain-mutations","display_name":"kinase domain mutations","score":0.7459999918937683},{"id":"https://openalex.org/keywords/structural-modeling","display_name":"structural modeling","score":0.5090000033378601},{"id":"https://openalex.org/keywords/ba-f3-cells","display_name":"Ba/F3 cells","score":0.6499999761581421}],"concepts":[{"id":"https://openalex.org/C2775999482","wikidata":"https://www.wikidata.org/wiki/Q18031208","display_name":"ROS1","level":4,"score":0.6667542457580566},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.5885219573974609},{"id":"https://openalex.org/C57473165","wikidata":"https://www.wikidata.org/wiki/Q7315604","display_name":"Resistance (ecology)","level":2,"score":0.4682159423828125},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3848552405834198},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.33723700046539307},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.28323841094970703},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2439599633216858},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.17559275031089783},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.17245885729789734},{"id":"https://openalex.org/C18903297","wikidata":"https://www.wikidata.org/wiki/Q7150","display_name":"Ecology","level":1,"score":0.10126566886901855},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.06885921955108643},{"id":"https://openalex.org/C2781182431","wikidata":"https://www.wikidata.org/wiki/Q356033","display_name":"Adenocarcinoma","level":3,"score":0.06315872073173523}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1158/1535-7163.c.6543498","doi":"https://doi.org/10.1158/1535-7163.c.6543498","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543498","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},{"id":"doi:10.1158/1535-7163.c.6543498.v1","doi":"https://doi.org/10.1158/1535-7163.c.6543498.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/1535-7163.c.6543498.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/1535-7163.c.6543498","doi":"https://doi.org/10.1158/1535-7163.c.6543498","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.6543498","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4200087860","https://openalex.org/W3083720088","https://openalex.org/W2944929814","https://openalex.org/W4409632723","https://openalex.org/W4385311627","https://openalex.org/W7148635733","https://openalex.org/W7165774746","https://openalex.org/W2981589800","https://openalex.org/W4389227476","https://openalex.org/W4234361637"],"abstract_inverted_index":{"Abstract":[0],"ROS1":[1,10,44,69,194],"fusion":[2,70],"proteins":[3],"resulting":[4],"from":[5],"chromosomal":[6],"rearrangements":[7],"of":[8,43,65,133,138,188,212],"the":[9,41,63,182],"gene":[11],"are":[12,58,164],"targetable":[13],"oncogenic":[14],"drivers":[15],"in":[16,51,62,81,108],"diverse":[17],"cancers.":[18],"Acquired":[19],"resistance":[20,89],"to":[21,87,91,130,151,159,166,181,209],"targeted":[22,33],"inhibitors":[23,204],"curtails":[24],"clinical":[25],"benefit":[26],"and":[27,56,84,94,104,110,114,127,171,173,201],"response":[28],"durability.":[29],"Entrectinib,":[30],"a":[31,99,121],"NTRK/ROS1/ALK":[32],"tyrosine":[34],"kinase":[35,142],"inhibitor":[36],"(TKI),":[37],"was":[38,106],"approved":[39],"for":[40],"treatment":[42],"fusion-positive":[45],"non\u2013small":[46],"cell":[47],"lung":[48],"cancer":[49],"(NSCLC)":[50],"2019.":[52],"In":[53],"addition,":[54],"lorlatinib":[55],"repotrectinib":[57],"actively":[59],"being":[60],"explored":[61],"setting":[64],"treatment-na\u00efve":[66],"or":[67,196],"crizotinib-resistant":[68],"driven":[71],"NSCLC.":[72],"Here,":[73],"we":[74],"employed":[75],"an":[76],"unbiased":[77],"forward":[78],"mutagenesis":[79],"screen":[80],"Ba/F3":[82],"CD74-ROS1":[83],"EZR-ROS1":[85],"cells":[86],"identify":[88],"liabilities":[90],"entrectinib,":[92],"lorlatinib,":[93],"repotrectinib.":[95],"ROS1F2004C":[96],"emerged":[97],"as":[98],"recurrent":[100],"entrectinib":[101,109,119,170],"resistant":[102,134,150,165],"mutation":[103],"ROS1G2032R":[105],"discovered":[107],"lorlatinib-resistant":[111],"clones.":[112],"Cell-based":[113],"modeling":[115],"data":[116],"show":[117],"that":[118,146],"is":[120,148],"dual":[122],"type":[123,153,160,167,174,183,192,199,202],"I/II":[124],"mode":[125],"inhibitor,":[126,176],"thus":[128],"liable":[129],"both":[131],"types":[132],"mutations.":[135],"Comprehensive":[136],"profiling":[137],"all":[139,152],"clinically":[140],"relevant":[141],"domain":[143],"mutations":[144],"showed":[145],"ROS1L2086F":[147],"broadly":[149],"I":[154,168,184,200],"inhibitors,":[155,169],"but":[156,178],"remains":[157],"sensitive":[158],"II":[161,175,193,203],"inhibitors.":[162,186],"ROS1F2004C/I/V":[163],"crizotinib,":[172],"cabozantinib,":[177],"retain":[179],"sensitivity":[180],"macrocyclic":[185],"Development":[187],"new,":[189],"more":[190],"selective":[191],"inhibitor(s)":[195],"potentially":[197],"cycling":[198],"may":[205],"be":[206],"one":[207],"way":[208],"expand":[210],"durability":[211],"ROS1-targeted":[213],"agents.":[214]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2024-03-13T00:00:00"}
