{"id":"https://openalex.org/W2012841672","doi":"https://doi.org/10.1158/0008-5472.can-05-4602","title":"Identification of an Agent Selectively Targeting DPC4 (Deleted in Pancreatic Cancer Locus 4)\u2013Deficient Pancreatic Cancer Cells","display_name":"Identification of an Agent Selectively Targeting DPC4 (Deleted in Pancreatic Cancer Locus 4)\u2013Deficient Pancreatic Cancer Cells","publication_year":2006,"publication_date":"2006-10-01","ids":{"openalex":"https://openalex.org/W2012841672","doi":"https://doi.org/10.1158/0008-5472.can-05-4602","mag":"2012841672","pmid":"https://pubmed.ncbi.nlm.nih.gov/17018631"},"language":"en","primary_location":{"id":"doi:10.1158/0008-5472.can-05-4602","doi":"https://doi.org/10.1158/0008-5472.can-05-4602","is_oa":false,"landing_page_url":"https://doi.org/10.1158/0008-5472.can-05-4602","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100370968","display_name":"Hong Wang","orcid":"https://orcid.org/0000-0003-0212-5379","observed_orcids":["https://orcid.org/0000-0003-0212-5379"]},"institutions":[{"id":"https://openalex.org/I1284308235","display_name":"Translational Genomics Research Institute","ror":"https://ror.org/02hfpnk21","country_code":"US","type":"facility","lineage":["https://openalex.org/I1284308235"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hong Wang","raw_affiliation_strings":["The Translational Genomics Research Institute, Phoenix, Arizona","Pancreatic Cancer Research Laboratory, Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Translational Genomics Research Institute, Phoenix, Arizona","institution_ids":["https://openalex.org/I1284308235"]},{"raw_affiliation_string":"Pancreatic Cancer Research Laboratory, Clinical Translational Research Division, Translational Genomics Research Institute, Phoenix, AZ 85004, USA","institution_ids":["https://openalex.org/I1284308235"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5037894273","display_name":"Haiyong Han","orcid":"https://orcid.org/0000-0001-9031-9880","observed_orcids":["https://orcid.org/0000-0001-9031-9880"]},"institutions":[{"id":"https://openalex.org/I1284308235","display_name":"Translational Genomics Research Institute","ror":"https://ror.org/02hfpnk21","country_code":"US","type":"facility","lineage":["https://openalex.org/I1284308235"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Haiyong Han","raw_affiliation_strings":["The Translational Genomics Research Institute, Phoenix, Arizona"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Translational Genomics Research Institute, Phoenix, Arizona","institution_ids":["https://openalex.org/I1284308235"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5080900202","display_name":"Daniel D. Von Hoff","orcid":"https://orcid.org/0000-0003-4723-7681","observed_orcids":["https://orcid.org/0000-0003-4723-7681"]},"institutions":[{"id":"https://openalex.org/I1284308235","display_name":"Translational Genomics Research Institute","ror":"https://ror.org/02hfpnk21","country_code":"US","type":"facility","lineage":["https://openalex.org/I1284308235"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel D. Von Hoff","raw_affiliation_strings":["The Translational Genomics Research Institute, Phoenix, Arizona"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Translational Genomics Research Institute, Phoenix, Arizona","institution_ids":["https://openalex.org/I1284308235"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1284308235"],"apc_list":null,"apc_paid":null,"fwci":1.9071,"has_fulltext":false,"cited_by_count":73,"citation_normalized_percentile":{"value":0.84701971,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":93,"max":99},"biblio":{"volume":"66","issue":"19","first_page":"9722","last_page":"9730"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9907000064849854,"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"}},"topics":[{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.9907000064849854,"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"}},{"id":"https://openalex.org/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.0010000000474974513,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.0007999999797903001,"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/smad4","display_name":"SMAD4","score":0.9729999899864197},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.9459999799728394},{"id":"https://openalex.org/keywords/loss-of-function-variants","display_name":"loss-of-function mutations","score":0.7979999780654907},{"id":"https://openalex.org/keywords/tumor-suppressor-genes","display_name":"tumor suppressor","score":0.906000018119812},{"id":"https://openalex.org/keywords/isogenic-cell-lines","display_name":"isogenic cell lines","score":0.7870000004768372},{"id":"https://openalex.org/keywords/compound-screening","display_name":"compound screening","score":0.6840000152587891},{"id":"https://openalex.org/keywords/cell-cycle-arrest","display_name":"cell cycle arrest","score":0.8330000042915344},{"id":"https://openalex.org/keywords/minichromosome-maintenance-complex","display_name":"minichromosome maintenance complex","score":0.9300000071525574},{"id":"https://openalex.org/keywords/bxpc-3-cells","display_name":"BxPC-3 cells","score":0.7429999709129333}],"concepts":[{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.7336552143096924},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.7084220051765442},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6338933110237122},{"id":"https://openalex.org/C105951970","wikidata":"https://www.wikidata.org/wiki/Q1036748","display_name":"Loss function","level":4,"score":0.6077591180801392},{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.5568114519119263},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5350398421287537},{"id":"https://openalex.org/C2778502085","wikidata":"https://www.wikidata.org/wiki/Q7662767","display_name":"Synthetic lethality","level":4,"score":0.49729517102241516},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.47318315505981445},{"id":"https://openalex.org/C2778264664","wikidata":"https://www.wikidata.org/wiki/Q422445","display_name":"Tumor suppressor gene","level":4,"score":0.46478840708732605},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.4446377754211426},{"id":"https://openalex.org/C2780265364","wikidata":"https://www.wikidata.org/wiki/Q5009957","display_name":"CDKN2A","level":3,"score":0.42867010831832886},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.36483103036880493},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.3158791959285736},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.2864781320095062},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.18940743803977966}],"mesh":[{"descriptor_ui":"D000230","descriptor_name":"Adenocarcinoma","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D000230","descriptor_name":"Adenocarcinoma","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D000880","descriptor_name":"Anthraquinones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D000970","descriptor_name":"Antineoplastic Agents","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D004354","descriptor_name":"Drug Screening Assays, Antitumor","qualifier_ui":"Q000379","qualifier_name":"methods","is_major_topic":true},{"descriptor_ui":"D005240","descriptor_name":"Feasibility Studies","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005347","descriptor_name":"Fibroblasts","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007191","descriptor_name":"Indazoles","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D009363","descriptor_name":"Neoplasm Proteins","qualifier_ui":"Q000172","qualifier_name":"deficiency","is_major_topic":true},{"descriptor_ui":"D009363","descriptor_name":"Neoplasm Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D010190","descriptor_name":"Pancreatic Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D010190","descriptor_name":"Pancreatic Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D011993","descriptor_name":"Recombinant Fusion Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D016195","descriptor_name":"G2 Phase","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D016196","descriptor_name":"S Phase","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D016203","descriptor_name":"CDC2 Protein Kinase","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D019926","descriptor_name":"Cyclin B","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D020133","descriptor_name":"Reverse Transcriptase Polymerase Chain Reaction","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020411","descriptor_name":"Oligonucleotide Array Sequence Analysis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D020869","descriptor_name":"Gene Expression Profiling","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D034622","descriptor_name":"RNA Interference","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D034741","descriptor_name":"RNA, Small Interfering","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D051901","descriptor_name":"Smad4 Protein","qualifier_ui":"Q000172","qualifier_name":"deficiency","is_major_topic":true},{"descriptor_ui":"D051901","descriptor_name":"Smad4 Protein","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1158/0008-5472.can-05-4602","doi":"https://doi.org/10.1158/0008-5472.can-05-4602","is_oa":false,"landing_page_url":"https://doi.org/10.1158/0008-5472.can-05-4602","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},{"id":"pmid:17018631","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/17018631","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,"listed_in":[],"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":"Cancer research","raw_type":"Evaluation Study"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","score":0.7699999809265137,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G6665544905","display_name":"Targets to Therapeutics in Pancreatic Cancer","funder_award_id":"P01CA109552","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":55,"referenced_works":["https://openalex.org/W58478469","https://openalex.org/W125577685","https://openalex.org/W991789247","https://openalex.org/W1530814332","https://openalex.org/W1593019308","https://openalex.org/W1594245582","https://openalex.org/W1859252938","https://openalex.org/W1899713877","https://openalex.org/W1940496546","https://openalex.org/W1972818536","https://openalex.org/W1973268287","https://openalex.org/W1975980654","https://openalex.org/W1981589551","https://openalex.org/W1983338915","https://openalex.org/W1992668179","https://openalex.org/W1992933633","https://openalex.org/W2007963495","https://openalex.org/W2009007206","https://openalex.org/W2010397777","https://openalex.org/W2016086822","https://openalex.org/W2017289276","https://openalex.org/W2019299732","https://openalex.org/W2033345138","https://openalex.org/W2036933656","https://openalex.org/W2037386039","https://openalex.org/W2038531883","https://openalex.org/W2040063578","https://openalex.org/W2048248981","https://openalex.org/W2051976556","https://openalex.org/W2057632732","https://openalex.org/W2059330620","https://openalex.org/W2065339586","https://openalex.org/W2072931850","https://openalex.org/W2075863736","https://openalex.org/W2081794928","https://openalex.org/W2090011073","https://openalex.org/W2106762061","https://openalex.org/W2116867733","https://openalex.org/W2118909720","https://openalex.org/W2124156743","https://openalex.org/W2126909443","https://openalex.org/W2129560190","https://openalex.org/W2135352785","https://openalex.org/W2136270229","https://openalex.org/W2144042585","https://openalex.org/W2151922790","https://openalex.org/W2162525969","https://openalex.org/W2169790726","https://openalex.org/W2279017153","https://openalex.org/W2318686332","https://openalex.org/W2331081187","https://openalex.org/W2412656108","https://openalex.org/W2415940217","https://openalex.org/W4244515336","https://openalex.org/W6640695489"],"related_works":["https://openalex.org/W1994301634","https://openalex.org/W2327167094","https://openalex.org/W2078218551","https://openalex.org/W2326257516","https://openalex.org/W1987338076","https://openalex.org/W2002401237","https://openalex.org/W2973217137","https://openalex.org/W2092145769","https://openalex.org/W2056110983","https://openalex.org/W7045737977"],"abstract_inverted_index":{"One":[0],"of":[1,6,74,90,109,181,231,255],"the":[2,12,55,72,88,107,133,168,251],"most":[3],"common":[4],"types":[5],"genetic":[7],"alterations":[8],"in":[9,15,57,64,112,132,167,178,197,224],"cancer":[10,25,59,66,95,115,201],"is":[11],"loss-of-function":[13,44,98],"mutations":[14,19,45],"tumor-suppressor":[16],"genes.":[17],"Such":[18],"are":[20],"usually":[21],"very":[22],"specific":[23],"to":[24,138],"cells":[26,96,223],"and":[27,30,145,211,226,236,245],"present":[28],"attractive":[29],"unique":[31],"opportunities":[32],"for":[33,37,87,142],"therapeutic":[34],"interventions.":[35],"However,":[36],"various":[38],"reasons,":[39],"antitumor":[40],"agents":[41,91],"that":[42,92,220,242],"target":[43,94],"have":[46,81],"not":[47],"been":[48],"readily":[49],"identified.":[50],"In":[51,192],"this":[52],"report,":[53],"using":[54],"deleted":[56],"pancreatic":[58,65,114,200],"locus":[60],"4":[61],"(DPC4)":[62],"gene":[63,121,233],"as":[67],"an":[68],"example,":[69],"we":[70,80,154],"show":[71],"feasibility":[73],"a":[75,113],"novel":[76],"screening":[77,151],"strategy,":[78],"which":[79,160],"named":[82],"Pharmacological":[83,134],"Synthetic":[84,135],"Lethal":[85,136],"Screening,":[86],"identification":[89],"selectively":[93],"with":[97],"mutations.":[99],"We":[100],"created":[101],"DPC4":[102,111,120,148,165,169,182,209],"isogenic":[103,126,170,183],"cell":[104,116,127,171,184,202],"lines":[105,128,185],"through":[106],"restoration":[108],"wild-type":[110],"line,":[117],"BxPC-3,":[118],"whose":[119],"was":[122,175,195,214],"homozygously":[123],"deleted.":[124],"The":[125,229],"were":[129],"then":[130],"used":[131,199],"Screening":[137],"evaluate":[139],"compound":[140],"libraries":[141],"antiproliferative":[143],"activity":[144],"selectivity":[146,163,174],"against":[147,164],"deficiency.":[149],"After":[150],"19,590":[152],"compounds,":[153],"identified":[155],"one":[156],"lead":[157],"compound,":[158],"UA62001,":[159],"showed":[161],"4.6-fold":[162],"deficiency":[166,210],"lines.":[172,203],"UA62001":[173,194,212,221],"also":[176],"seen":[177],"another":[179],"set":[180],"generated":[186],"by":[187],"small":[188],"interfering":[189],"RNA":[190],"knockdown.":[191],"addition,":[193],"evaluated":[196],"commonly":[198],"A":[204],"fairly":[205],"good":[206],"correlation":[207],"between":[208],"sensitivity":[213],"observed.":[215],"Cell":[216],"cycle":[217],"analysis":[218],"indicates":[219],"arrests":[222],"S":[225],"G(2)-M":[227],"phases.":[228],"results":[230],"microarray":[232],"expression":[234],"profiling":[235],"quantitative":[237],"real-time":[238],"reverse":[239],"transcription-PCR":[240],"suggest":[241],"cyclin":[243],"B/CDC2":[244],"minichromosome":[246],"maintenance":[247],"complexes":[248],"might":[249],"be":[250],"downstream":[252],"cellular":[253],"targets":[254],"UA62001.":[256]},"counts_by_year":[{"year":2026,"cited_by_count":2},{"year":2025,"cited_by_count":2},{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":8},{"year":2022,"cited_by_count":5},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":5},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":2},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":4},{"year":2013,"cited_by_count":4},{"year":2012,"cited_by_count":3}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}