{"id":"https://openalex.org/W4281787488","doi":"https://doi.org/10.1101/2022.06.08.495301","title":"Loss of Spindly sensitizes EML4-ALK v3 lung cancer cells to HSP90 inhibitors","display_name":"Loss of Spindly sensitizes EML4-ALK v3 lung cancer cells to HSP90 inhibitors","publication_year":2022,"publication_date":"2022-06-08","ids":{"openalex":"https://openalex.org/W4281787488","doi":"https://doi.org/10.1101/2022.06.08.495301"},"language":"en","primary_location":{"id":"doi:10.1101/2022.06.08.495301","doi":"https://doi.org/10.1101/2022.06.08.495301","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.06.08.495301","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://doi.org/10.1101/2022.06.08.495301","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5025140172","display_name":"Marco P. Licciardello","orcid":"https://orcid.org/0000-0003-3197-4855","observed_orcids":["https://orcid.org/0000-0003-3197-4855"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]},{"id":"https://openalex.org/I2801316944","display_name":"Cancer Research UK","ror":"https://ror.org/054225q67","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I2801316944"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Marco P. Licciardello","raw_affiliation_strings":["Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom"],"raw_orcid":"https://orcid.org/0000-0003-3197-4855","affiliations":[{"raw_affiliation_string":"Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom","institution_ids":["https://openalex.org/I142947616","https://openalex.org/I2801316944"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100458161","display_name":"Chi Zhang","orcid":"https://orcid.org/0000-0002-1827-8137","observed_orcids":["https://orcid.org/0000-0002-1827-8137"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]},{"id":"https://openalex.org/I2801316944","display_name":"Cancer Research UK","ror":"https://ror.org/054225q67","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I2801316944"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Chi Zhang","raw_affiliation_strings":["Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom","institution_ids":["https://openalex.org/I142947616","https://openalex.org/I2801316944"]}]},{"author_position":"middle","author":{"id":null,"display_name":"Anh T. Le","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210134151","display_name":"University of Colorado Cancer Center","ror":"https://ror.org/04cqn7d42","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210134151"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Anh T. Le","raw_affiliation_strings":["University of Colorado Cancer Center, Aurora, Colorado, CO 80045, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Colorado Cancer Center, Aurora, Colorado, CO 80045, USA","institution_ids":["https://openalex.org/I4210134151"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5034705456","display_name":"Robert Charles Doebele","orcid":"https://orcid.org/0000-0001-6728-6857","observed_orcids":["https://orcid.org/0000-0001-6728-6857"]},"institutions":[{"id":"https://openalex.org/I4210134151","display_name":"University of Colorado Cancer Center","ror":"https://ror.org/04cqn7d42","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4210134151"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Robert C. Doebele","raw_affiliation_strings":["University of Colorado Cancer Center, Aurora, Colorado, CO 80045, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"University of Colorado Cancer Center, Aurora, Colorado, CO 80045, USA","institution_ids":["https://openalex.org/I4210134151"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042056024","display_name":"Paul Andrew Clarke","orcid":"https://orcid.org/0000-0001-9342-1290","observed_orcids":["https://orcid.org/0000-0001-9342-1290"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]},{"id":"https://openalex.org/I2801316944","display_name":"Cancer Research UK","ror":"https://ror.org/054225q67","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I2801316944"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Paul A. Clarke","raw_affiliation_strings":["Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom","institution_ids":["https://openalex.org/I142947616","https://openalex.org/I2801316944"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5003965204","display_name":"Paul Workman","orcid":"https://orcid.org/0000-0003-1659-3034","observed_orcids":["https://orcid.org/0000-0003-1659-3034"]},"institutions":[{"id":"https://openalex.org/I142947616","display_name":"Institute of Cancer Research","ror":"https://ror.org/043jzw605","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I142947616"]},{"id":"https://openalex.org/I2801316944","display_name":"Cancer Research UK","ror":"https://ror.org/054225q67","country_code":"GB","type":"nonprofit","lineage":["https://openalex.org/I2801316944"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Paul Workman","raw_affiliation_strings":["Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, SM2 5NG, United Kingdom","institution_ids":["https://openalex.org/I142947616","https://openalex.org/I2801316944"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5003965204"],"corresponding_institution_ids":["https://openalex.org/I142947616","https://openalex.org/I2801316944"],"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":0.7294999957084656,"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":0.7294999957084656,"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/T10934","display_name":"Heat shock proteins research","score":0.2290000021457672,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"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/T12334","display_name":"Lung Cancer Research Studies","score":0.010499999858438969,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/spindly","display_name":"SPINDLY","score":0.9240000247955322},{"id":"https://openalex.org/keywords/eml4-alk-fusion","display_name":"EML4-ALK fusion","score":0.875},{"id":"https://openalex.org/keywords/hsp90-inhibitors","display_name":"Hsp90 inhibitors","score":0.8870000243186951},{"id":"https://openalex.org/keywords/non-small-cell-lung-cancer","display_name":"non-small cell lung cancer","score":0.9890000224113464},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.6899999976158142},{"id":"https://openalex.org/keywords/chromosome-congression","display_name":"chromosome congression","score":0.8420000076293945},{"id":"https://openalex.org/keywords/crispr-cas9-knockout-screen","display_name":"CRISPR-Cas9 knockout screen","score":0.8920000195503235},{"id":"https://openalex.org/keywords/tumor-suppressor-loss","display_name":"tumor suppressor loss","score":0.4399999976158142}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6616547703742981},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.5325901508331299},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5129944682121277},{"id":"https://openalex.org/C2779177807","wikidata":"https://www.wikidata.org/wiki/Q3658562","display_name":"non-small cell lung cancer (NSCLC)","level":4,"score":0.4453238844871521},{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.44022461771965027},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.34926262497901917},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.25031620264053345},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.22631007432937622},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.16073033213615417},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.15054810047149658},{"id":"https://openalex.org/C81729549","wikidata":"https://www.wikidata.org/wiki/Q4649475","display_name":"A549 cell","level":3,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1101/2022.06.08.495301","doi":"https://doi.org/10.1101/2022.06.08.495301","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.06.08.495301","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1101/2022.06.08.495301","doi":"https://doi.org/10.1101/2022.06.08.495301","is_oa":true,"landing_page_url":"https://doi.org/10.1101/2022.06.08.495301","pdf_url":null,"source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9537000060081482}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.8299999833106995}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":57,"referenced_works":["https://openalex.org/W1535278128","https://openalex.org/W1915513909","https://openalex.org/W1973260880","https://openalex.org/W1988533633","https://openalex.org/W1992446787","https://openalex.org/W1992909271","https://openalex.org/W2001673920","https://openalex.org/W2006564825","https://openalex.org/W2007877171","https://openalex.org/W2025396651","https://openalex.org/W2026002143","https://openalex.org/W2029335488","https://openalex.org/W2029663913","https://openalex.org/W2050393309","https://openalex.org/W2050654618","https://openalex.org/W2050723856","https://openalex.org/W2051278182","https://openalex.org/W2074187311","https://openalex.org/W2075447540","https://openalex.org/W2079900102","https://openalex.org/W2084582562","https://openalex.org/W2084687092","https://openalex.org/W2089686334","https://openalex.org/W2100541925","https://openalex.org/W2102824402","https://openalex.org/W2108590463","https://openalex.org/W2111361612","https://openalex.org/W2114032749","https://openalex.org/W2114843025","https://openalex.org/W2119854781","https://openalex.org/W2130410032","https://openalex.org/W2134160832","https://openalex.org/W2136245016","https://openalex.org/W2142919879","https://openalex.org/W2153387139","https://openalex.org/W2162107265","https://openalex.org/W2162343852","https://openalex.org/W2252568502","https://openalex.org/W2274015824","https://openalex.org/W2482427906","https://openalex.org/W2566859523","https://openalex.org/W2601242282","https://openalex.org/W2601885162","https://openalex.org/W2751382641","https://openalex.org/W2771414687","https://openalex.org/W2902031310","https://openalex.org/W2903022477","https://openalex.org/W2903181389","https://openalex.org/W2936686072","https://openalex.org/W2951171917","https://openalex.org/W2978074062","https://openalex.org/W3011331060","https://openalex.org/W3016713427","https://openalex.org/W3047187942","https://openalex.org/W3148211770","https://openalex.org/W3155633297","https://openalex.org/W4281725417"],"related_works":["https://openalex.org/W2050654618","https://openalex.org/W2887308675","https://openalex.org/W2764830621","https://openalex.org/W2020273923","https://openalex.org/W2136245016","https://openalex.org/W1607235472","https://openalex.org/W1601293742","https://openalex.org/W2177936014","https://openalex.org/W2166292499","https://openalex.org/W2338477466"],"abstract_inverted_index":{"Heat":[0],"Shock":[1],"Protein":[2],"90":[3],"inhibitors":[4],"(HSP90i)":[5],"have":[6,21,33],"shown":[7],"activity":[8],"in":[9,62,77,142],"EML4-ALK":[10,30,53,97,143],"+":[11],"non-small":[12],"cell":[13],"lung":[14],"cancer":[15],"(NSCLC)":[16],"patients":[17,146],"but":[18,99],"clinical":[19],"responses":[20],"been":[22,26],"heterogeneous.":[23],"It":[24],"has":[25],"suggested":[27],"that":[28,46,73,89,135],"distinct":[29,111],"variants":[31],"may":[32,147],"a":[34,82],"differential":[35],"impact":[36],"on":[37],"the":[38,50,94],"response":[39],"to":[40,66,104,120,138,150],"HSP90":[41],"inhibition.":[42],"Here,":[43],"we":[44,80],"show":[45],"NSCLC":[47,102,145],"cells":[48,103],"harboring":[49],"most":[51],"common":[52],"variant":[54,58],"1":[55],"(v1)":[56],"or":[57],"3":[59],"(v3)":[60],"are":[61],"fact":[63],"similarly":[64],"sensitive":[65],"HSP90i.":[67,154],"To":[68],"discover":[69],"new":[70],"genetic":[71],"alterations":[72],"could":[74],"be":[75],"involved":[76],"stratifying":[78],"sensitivity,":[79],"performed":[81],"genome-wide":[83],"CRISPR/Cas9":[84],"knockout":[85],"screen":[86],"and":[87,128],"found":[88],"loss":[90,115,139],"of":[91,96,107,116,123,140,153],"Spindly":[92,141],"increases":[93],"sensitivity":[95,149],"v3,":[98],"not":[100],"v1,":[101],"low":[105,121,151],"concentrations":[106,122],"HSP90i":[108,124],"from":[109],"three":[110],"chemical":[112],"families.":[113],"Upon":[114],"Spindly,":[117],"prolonged":[118],"exposure":[119],"impairs":[125],"chromosome":[126],"congression":[127],"cellular":[129],"fitness.":[130],"Collectively,":[131],"our":[132],"data":[133],"suggest":[134],"mutations":[136],"leading":[137],"v3":[144],"increase":[148],"doses":[152]},"counts_by_year":[],"updated_date":"2026-10-16T09:59:22.235173","created_date":"2022-06-13T00:00:00"}
