{"id":"https://openalex.org/W4362592259","doi":"https://doi.org/10.1158/1538-7445.am2023-4343","title":"Abstract 4343: Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to EGFR inhibitors","display_name":"Abstract 4343: Development of an APC and TP53-based duplex sequencing assay to positively predict colorectal cancer response to EGFR inhibitors","publication_year":2023,"publication_date":"2023-04-04","ids":{"openalex":"https://openalex.org/W4362592259","doi":"https://doi.org/10.1158/1538-7445.am2023-4343"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2023-4343","doi":"https://doi.org/10.1158/1538-7445.am2023-4343","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2023-4343","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":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"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/A5002006406","display_name":"Mingli Yang","orcid":"https://orcid.org/0000-0002-4781-690X","observed_orcids":["https://orcid.org/0000-0002-4781-690X"]},"institutions":[{"id":"https://openalex.org/I2613432","display_name":"University of South Florida","ror":"https://ror.org/032db5x82","country_code":"US","type":"education","lineage":["https://openalex.org/I2613432"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Mingli Yang","raw_affiliation_strings":["1University of South Florida, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Florida, Tampa, FL;","institution_ids":["https://openalex.org/I2613432"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061312918","display_name":"Michael J. Schell","orcid":"https://orcid.org/0000-0003-4594-6601","observed_orcids":["https://orcid.org/0000-0003-4594-6601","https://orcid.org/0000-0003-1553-3582"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Michael J. Schell","raw_affiliation_strings":["2Moffitt Cancer Center and Research Institute, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Moffitt Cancer Center and Research Institute, Tampa, FL;","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060853762","display_name":"Lance T. Pflieger","orcid":"https://orcid.org/0000-0003-2237-5674","observed_orcids":["https://orcid.org/0000-0003-2237-5674"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lance Pflieger","raw_affiliation_strings":["3Phenome Health, Seattle, WA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"3Phenome Health, Seattle, WA;","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5054082017","display_name":"Jesse J. Salk","orcid":"https://orcid.org/0000-0002-7804-0550","observed_orcids":["https://orcid.org/0000-0002-7804-0550"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jesse Salk","raw_affiliation_strings":["4TwinStrand Biosciences, Seattle, WA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"4TwinStrand Biosciences, Seattle, WA","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5113849367","display_name":"Timothy Joseph Yeatman","orcid":"https://orcid.org/0000-0002-7487-0784","observed_orcids":["https://orcid.org/0000-0002-7487-0784"]},"institutions":[{"id":"https://openalex.org/I2613432","display_name":"University of South Florida","ror":"https://ror.org/032db5x82","country_code":"US","type":"education","lineage":["https://openalex.org/I2613432"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Timothy J. Yeatman","raw_affiliation_strings":["1University of South Florida, Tampa, FL;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1University of South Florida, Tampa, FL;","institution_ids":["https://openalex.org/I2613432"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"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":"83","issue":"7_Supplement","first_page":"4343","last_page":"4343"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.9814000129699707,"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/T11067","display_name":"Colorectal Cancer Treatments and Studies","score":0.9814000129699707,"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/T11287","display_name":"Cancer Genomics and Diagnostics","score":0.009399999864399433,"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/T11369","display_name":"Genetic factors in colorectal cancer","score":0.004900000058114529,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic 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/colorectal-cancer","display_name":"colorectal cancer","score":0.800000011920929},{"id":"https://openalex.org/keywords/egfr-inhibitors","display_name":"EGFR inhibitors","score":0.9869999885559082},{"id":"https://openalex.org/keywords/cetuximab","display_name":"cetuximab","score":0.8989999890327454},{"id":"https://openalex.org/keywords/panitumumab","display_name":"panitumumab","score":0.8930000066757202},{"id":"https://openalex.org/keywords/apc-mutation","display_name":"APC mutation","score":0.9049999713897705},{"id":"https://openalex.org/keywords/tp53-mutation","display_name":"TP53 mutation","score":1.0},{"id":"https://openalex.org/keywords/duplex-sequencing","display_name":"duplex sequencing","score":0.7839999794960022},{"id":"https://openalex.org/keywords/predictive-biomarkers","display_name":"predictive biomarkers","score":0.6010000109672546},{"id":"https://openalex.org/keywords/kras","display_name":"KRAS","score":0.6069999933242798},{"id":"https://openalex.org/keywords/braf","display_name":"BRAF","score":0.9909999966621399},{"id":"https://openalex.org/keywords/nras","display_name":"NRAS","score":0.9610000252723694},{"id":"https://openalex.org/keywords/hras","display_name":"HRAS","score":0.996999979019165},{"id":"https://openalex.org/keywords/ras-raf-mutations","display_name":"RAS/RAF mutations","score":0.5889999866485596},{"id":"https://openalex.org/keywords/formalin-fixed-paraffin-embedded-tissue","display_name":"formalin-fixed paraffin-embedded tissue","score":0.5389999747276306},{"id":"https://openalex.org/keywords/assay-validation","display_name":"assay validation","score":0.43299999833106995},{"id":"https://openalex.org/keywords/gene-expression-signatures","display_name":"gene expression signatures","score":0.5299999713897705},{"id":"https://openalex.org/keywords/metastatic-colorectal-cancer","display_name":"metastatic colorectal cancer","score":0.6470000147819519},{"id":"https://openalex.org/keywords/targeted-therapy","display_name":"targeted therapy","score":0.328000009059906}],"concepts":[{"id":"https://openalex.org/C2779998722","wikidata":"https://www.wikidata.org/wiki/Q420296","display_name":"Cetuximab","level":4,"score":0.899277925491333},{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.8778936862945557},{"id":"https://openalex.org/C2778332735","wikidata":"https://www.wikidata.org/wiki/Q417775","display_name":"Panitumumab","level":5,"score":0.7797761559486389},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.6758558750152588},{"id":"https://openalex.org/C21790070","wikidata":"https://www.wikidata.org/wiki/Q18030215","display_name":"Neuroblastoma RAS viral oncogene homolog","level":5,"score":0.6726658344268799},{"id":"https://openalex.org/C1167327","wikidata":"https://www.wikidata.org/wiki/Q14884140","display_name":"HRAS","level":5,"score":0.592621922492981},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.5921809673309326},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5523232221603394},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5104562044143677},{"id":"https://openalex.org/C2781197716","wikidata":"https://www.wikidata.org/wiki/Q864574","display_name":"Biomarker","level":2,"score":0.48470568656921387},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3851797580718994},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3741319477558136},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2304036021232605},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.19467788934707642}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2023-4343","doi":"https://doi.org/10.1158/1538-7445.am2023-4343","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.am2023-4343","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"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":0.9763000011444092}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7123344903","https://openalex.org/W2885192016","https://openalex.org/W2941836269","https://openalex.org/W4282979833","https://openalex.org/W2889668690","https://openalex.org/W3030815613","https://openalex.org/W4391096101","https://openalex.org/W1865727470","https://openalex.org/W4405901813","https://openalex.org/W3209858902"],"abstract_inverted_index":{"Abstract":[0],"Two":[1],"well-characterized":[2],"EGFR":[3,452],"inhibitor":[4],"(EGFRi)":[5],"therapies":[6],"(cetuximab,":[7],"panitumumab)":[8],"have":[9,371],"been":[10,169],"FDA":[11],"approved":[12],"for":[13,134,162,200,206,260,461],"metastatic":[14],"colorectal":[15,448],"cancer":[16,449],"(CRC).":[17],"Unfortunately,":[18],"the":[19,25,139,239,264,339,346,354,458],"extended":[20],"RAS/RAF":[21],"testing":[22],"required":[23],"in":[24,73,89,218,229,238,245],"drug":[26],"labels,":[27],"identifies":[28],"only":[29,32],"non-responders,":[30],"and":[31,64,75,158,250,363,381,392,405,440,470],"~50%":[33],"of":[34,107,326,338,407,437,457],"treated":[35],"patients":[36,126,276,359],"will":[37],"respond":[38],"to":[39,47,51,116,122,129,181,310,353,370,401,409,445,451],"therapy.":[40],"Thus,":[41,396],"there":[42,397],"is":[43,394,398,420],"an":[44,57,148,399,438],"unmet":[45],"need":[46],"develop":[48,117],"additional":[49,302],"biomarkers":[50],"identify":[52],"EGFRi":[53,341],"sensitive":[54,418],"patients.":[55,136],"Using":[56],"innovative":[58],"hybrid":[59],"approach":[60],"fusing":[61],"gene":[62,83],"expression":[63,84],"DNA":[65,119],"sequencing,":[66],"we":[67,145],"recently":[68,146],"reported":[69],"that":[70,344],"combined":[71,361],"mutations":[72,214,236,304,319,329],"APC":[74,108,362,439],"TP53":[76,110,364],"were":[77,178,216],"strongly":[78],"correlated":[79],"with":[80],"a":[81,102,118,311],"validated":[82,171],"signature":[85],"measuring":[86],"cetuximab":[87],"sensitivity":[88,211],"CRC":[90,135,164,275,412],"human":[91],"tumors":[92],"(Yang":[93],"et":[94],"al.":[95],"Cancer":[96,462,481],"Epidemiol":[97],"Biomarkers":[98],"Prev.":[99],"2019),":[100],"suggesting":[101],"potential":[103],"positive":[104],"biomarker":[105],"role":[106],"+":[109],"mutations.":[111],"This":[112],"finding":[113],"prompted":[114],"us":[115],"test":[120,419],"designed":[121],"positively":[123,446],"select":[124],"EGFRi-responsive":[125],"as":[127],"augmentation":[128],"currently":[130],"used":[131],"negative":[132],"predictors":[133],"By":[137],"leveraging":[138],"TwinStrand":[140,315],"Duplex":[141,183,201],"Sequencing":[142],"(DS)":[143],"technology,":[144],"developed":[147],"ultrasensitive":[149,296],"custom":[150],"6-gene":[151,186,280],"panel":[152],"(APC,":[153],"TP53,":[154],"KRAS,":[155],"BRAF,":[156],"NRAS,":[157],"HRAS)":[159],"CLIA-certified":[160],"assay":[161,167,188,192,282,289,298,444],"FFPE":[163,285],"tissues.":[165],"The":[166,185,279,295],"has":[168],"analytically":[170],"using":[172],"reference":[173],"cell":[174],"lines":[175],"(n=10)":[176],"which":[177],"individually":[179],"sequenced":[180],">3,000x":[182],"depth.":[184],"DS":[187,281,297,316],"yielded":[189],"exceptionally":[190],"high":[191],"performance:":[193],"(1)":[194,278],"accuracy":[195],"(passed,":[196,212,234,253],"r2":[197],"=":[198],"0.98":[199],"VAF":[202,205,248,261],"vs.":[203],"target":[204],"Positive":[207,220,257],"Control":[208,221,241,258],"mutations);":[209],"(2)":[210,294],"all":[213,219],">1/5,000":[215],"detected":[217,228,237],"replicates;":[222],"1":[223,243,246,468],"mutation":[224],"at":[225,242,305],"1/5,000":[226],"was":[227,349],"2/3":[230],"replicates),":[231],"(3)":[232],"specificity":[233],"2":[235],"Negative":[240],"count":[244],"replicate;":[247],"<1/10,000),":[249],"(4)":[251],"precision":[252],"<2-fold":[254],"variation":[255],"among":[256],"replicates":[259],">1/500).":[262],"Importantly,":[263],"validation":[265],"analysis":[266,337,393],"on":[267,284,291],"fresh":[268],"frozen":[269],"(FF):FFPE":[270],"paired":[271],"tissues":[272],"from":[273],"21":[274],"shows:":[277],"performed":[283],"samples":[286],"faithfully":[287],"reproduces":[288],"results":[290],"FF":[292],"samples;":[293],"can":[299],"accurately":[300],"detect":[301],"\u201cnew\u201d":[303],"low":[306],"allelic":[307],"frequencies":[308],"compared":[309],"standard":[312,323],"NGS":[313],"method.":[314],"identified":[317,321],"17":[318],"not":[320,350],"by":[322],"NGS;":[324],"13":[325],"these":[327],"new":[328],"had":[330],"<":[331],"10%":[332],"VAF.":[333],"Furthermore,":[334],"preliminary":[335],"Kaplan-Meier":[336],"third-line":[340],"data":[342,390],"shows":[343],"while":[345],"statistical":[347],"significance":[348],"achieved":[351],"due":[352],"small":[355],"simple":[356],"size":[357],"(n=28),":[358],"harboring":[360],"mutations(AP)":[365],"(vs":[366],"non-AP":[367],"patients)":[368],"tended":[369],"longer":[372],"progression":[373],"free":[374],"survival":[375,383],"(6.65":[376],"vs":[377,385],"3.95":[378],"months,":[379,387],"P=0.064)":[380],"overall":[382],"(17.80":[384],"10.65":[386],"P=0.14).":[388],"Additional":[389],"acquisition":[391],"ongoing.":[395],"opportunity":[400],"change":[402],"clinical":[403],"practice":[404],"standards":[406],"care":[408],"ultimately":[410],"improve":[411],"outcomes":[413],"if":[414],"this":[415],"new,":[416],"robust,":[417],"clinically-validated.":[421],"Citation":[422],"Format:":[423],"Mingli":[424],"Yang,":[425],"Michael":[426],"J.":[427,434],"Schell,":[428],"Lance":[429],"Pflieger,":[430],"Jesse":[431],"Salk,":[432],"Timothy":[433],"Yeatman.":[435],"Development":[436],"TP53-based":[441],"duplex":[442],"sequencing":[443],"predict":[447],"response":[450],"inhibitors.":[453],"[abstract].":[454],"In:":[455],"Proceedings":[456],"American":[459],"Association":[460],"Research":[463],"Annual":[464],"Meeting":[465],"2023;":[466],"Part":[467],"(Regular":[469],"Invited":[471],"Abstracts);":[472],"2023":[473],"Apr":[474],"14-19;":[475],"Orlando,":[476],"FL.":[477],"Philadelphia":[478],"(PA):":[479],"AACR;":[480],"Res":[482],"2023;83(7_Suppl):Abstract":[483],"nr":[484],"4343.":[485]},"counts_by_year":[],"updated_date":"2026-10-01T08:54:57.152042","created_date":"2023-04-06T00:00:00"}