{"id":"https://openalex.org/W4361823707","doi":"https://doi.org/10.1158/0008-5472.c.6508554","title":"Data from Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4\u2013NDRG1 Axis","display_name":"Data from Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4\u2013NDRG1 Axis","publication_year":2023,"publication_date":"2023-03-31","ids":{"openalex":"https://openalex.org/W4361823707","doi":"https://doi.org/10.1158/0008-5472.c.6508554"},"language":"en","primary_location":{"id":"doi:10.1158/0008-5472.c.6508554","doi":"https://doi.org/10.1158/0008-5472.c.6508554","is_oa":true,"landing_page_url":"https://doi.org/10.1158/0008-5472.c.6508554","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","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1158/0008-5472.c.6508554","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5000072080","display_name":"Nandini Verma","orcid":"https://orcid.org/0000-0001-5260-8999","observed_orcids":["https://orcid.org/0000-0001-5260-8999"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nandini Verma","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103576430","display_name":"Anna\u2010Katharina M\u00fcller","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Anna-Katharina M\u00fcller","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5014237992","display_name":"Charu Kothari","orcid":"https://orcid.org/0000-0002-2704-5677","observed_orcids":["https://orcid.org/0000-0002-2704-5677"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Charu Kothari","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036424644","display_name":"Effrosini G. Panayotopoulou","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Effrosini Panayotopoulou","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5044210944","display_name":"Amir Kedan","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Amir Kedan","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5016667100","display_name":"Michael Selitrennik","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael Selitrennik","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005221518","display_name":"Gordon Brent Mills","orcid":"https://orcid.org/0000-0002-0144-9614","observed_orcids":["https://orcid.org/0000-0002-0144-9614"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gordon B. Mills","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5040251521","display_name":"Lan K. Nguyen","orcid":"https://orcid.org/0000-0003-4040-7705","observed_orcids":["https://orcid.org/0000-0003-4040-7705"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lan K. Nguyen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5079201651","display_name":"Sung\u2010Young Shin","orcid":"https://orcid.org/0000-0002-1447-9687","observed_orcids":["https://orcid.org/0000-0002-1447-9687"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sungyoung Shin","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5024589782","display_name":"Thomas Karn","orcid":"https://orcid.org/0000-0002-3264-6573","observed_orcids":["https://orcid.org/0000-0002-3264-6573"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Thomas Karn","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5026280934","display_name":"Uwe Holtrich","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Uwe Holtrich","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5051953963","display_name":"Sima Lev","orcid":"https://orcid.org/0000-0002-2108-3330","observed_orcids":["https://orcid.org/0000-0002-2108-3330"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sima Lev","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/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9955999851226807,"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/T10755","display_name":"HER2/EGFR in Cancer Research","score":0.9955999851226807,"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/T10183","display_name":"Breast Cancer Treatment Studies","score":0.002400000113993883,"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/T10952","display_name":"PI3K/AKT/mTOR signaling in cancer","score":0.000699999975040555,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.9269999861717224},{"id":"https://openalex.org/keywords/egfr-antagonists","display_name":"EGFR antagonists","score":0.9139999747276306},{"id":"https://openalex.org/keywords/pyk2","display_name":"Pyk2","score":0.9470000267028809},{"id":"https://openalex.org/keywords/focal-adhesion-kinase","display_name":"focal adhesion kinase","score":0.9520000219345093},{"id":"https://openalex.org/keywords/her3","display_name":"HER3","score":0.8659999966621399},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.8289999961853027},{"id":"https://openalex.org/keywords/nedd4","display_name":"NEDD4","score":0.9850000143051147},{"id":"https://openalex.org/keywords/ndrg1","display_name":"NDRG1","score":0.9990000128746033},{"id":"https://openalex.org/keywords/proteasomal-degradation","display_name":"proteasomal degradation","score":0.824999988079071},{"id":"https://openalex.org/keywords/compensatory-signaling","display_name":"compensatory signaling","score":0.6639999747276306},{"id":"https://openalex.org/keywords/akt","display_name":"Akt","score":0.6290000081062317},{"id":"https://openalex.org/keywords/stat3","display_name":"STAT3","score":0.9129999876022339},{"id":"https://openalex.org/keywords/erk1-2","display_name":"ERK1/2","score":0.9179999828338623},{"id":"https://openalex.org/keywords/ribosomal-protein-s6-kinase","display_name":"S6K","score":0.8429999947547913}],"concepts":[{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.7624468803405762},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7182554006576538},{"id":"https://openalex.org/C134459356","wikidata":"https://www.wikidata.org/wiki/Q4274835","display_name":"Ubiquitin ligase","level":4,"score":0.5699917078018188},{"id":"https://openalex.org/C2777506169","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"EGFR inhibitors","level":4,"score":0.5041865110397339},{"id":"https://openalex.org/C2779438470","wikidata":"https://www.wikidata.org/wiki/Q424401","display_name":"Epidermal growth factor receptor","level":3,"score":0.4364458918571472},{"id":"https://openalex.org/C42362537","wikidata":"https://www.wikidata.org/wiki/Q87099740","display_name":"Tyrosine kinase","level":3,"score":0.4275265038013458},{"id":"https://openalex.org/C2780110267","wikidata":"https://www.wikidata.org/wiki/Q7843332","display_name":"Triple-negative breast cancer","level":4,"score":0.42567867040634155},{"id":"https://openalex.org/C184235292","wikidata":"https://www.wikidata.org/wiki/Q421851","display_name":"Kinase","level":2,"score":0.41779425740242004},{"id":"https://openalex.org/C2778820342","wikidata":"https://www.wikidata.org/wiki/Q906415","display_name":"Tyrosine-kinase inhibitor","level":3,"score":0.4116875231266022},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4074404835700989},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.37187904119491577},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3466940224170685},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.34220200777053833},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.2512248158454895},{"id":"https://openalex.org/C25602115","wikidata":"https://www.wikidata.org/wiki/Q407111","display_name":"Ubiquitin","level":3,"score":0.23685723543167114},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.21410387754440308},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.07913157343864441},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07791891694068909},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.0}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1158/0008-5472.c.6508554","doi":"https://doi.org/10.1158/0008-5472.c.6508554","is_oa":true,"landing_page_url":"https://doi.org/10.1158/0008-5472.c.6508554","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:10.1158/0008-5472.c.6508554.v1","doi":"https://doi.org/10.1158/0008-5472.c.6508554.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/0008-5472.c.6508554.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:10.1158/0008-5472.c.6508554","doi":"https://doi.org/10.1158/0008-5472.c.6508554","is_oa":true,"landing_page_url":"https://doi.org/10.1158/0008-5472.c.6508554","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":0.98580002784729}],"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/W2544538072","https://openalex.org/W4320176274","https://openalex.org/W1994298503","https://openalex.org/W2134134362","https://openalex.org/W3105370941","https://openalex.org/W2057889906","https://openalex.org/W4214752223","https://openalex.org/W2991488941","https://openalex.org/W2043527891","https://openalex.org/W3083005781"],"abstract_inverted_index":{"Abstract":[0],"Triple-negative":[1],"breast":[2],"cancer":[3],"(TNBC)":[4],"is":[5,20,27],"a":[6,30,86,175,189,195],"highly":[7,21],"aggressive,":[8],"heterogeneous":[9],"disease":[10],"with":[11,54,152,161,166],"poor":[12],"prognosis":[13],"and":[14,26,65,81,94,100,108,163,183,201],"no":[15],"effective":[16],"targeted":[17],"therapies.":[18],"EGFR":[19,35,64,93,120,200],"expressed":[22],"in":[23,79,85,117,178],"basal-like":[24,76],"TNBC":[25,77,206],"considered":[28],"as":[29],"potential":[31],"therapeutic":[32],"target.":[33],"However,":[34],"targeting":[36,62,91],"exerts":[37],"only":[38],"marginal":[39],"clinical":[40],"benefits,":[41],"possibly":[42],"due":[43],"to":[44,119,204],"activation":[45],"of":[46,63,75,92,134,139,150,192,197],"compensatory":[47],"signaling":[48],"pathways,":[49],"which":[50,159],"are":[51],"frequently":[52],"associated":[53],"HER3":[55,115,135,151],"upregulation.":[56],"Here":[57],"we":[58],"show":[59],"that":[60,170],"concomitant":[61],"the":[66,73,131,148,153,171,199],"nonreceptor":[67],"tyrosine":[68],"kinases":[69,203],"PYK2/FAK":[70,95,202],"synergistically":[71],"inhibits":[72],"proliferation":[74],"cells":[78],"vitro":[80],"attenuates":[82],"tumor":[83],"growth":[84,99],"mouse":[87],"xenograft":[88],"model.":[89],"Dual":[90],"inhibited":[96],"complementary":[97],"key":[98],"survival":[101],"pathways":[102],"mediated":[103],"by":[104],"AKT,":[105],"S6K,":[106],"STAT3,":[107],"ERK1/2":[109],"activation.":[110],"PYK2":[111,128],"inhibition":[112,129],"also":[113],"abrogated":[114],"upregulation":[116,138],"response":[118],"antagonists,":[121],"thereby":[122],"circumventing":[123],"HER3-associated":[124],"drug":[125,181],"resistance.":[126],"Mechanistically,":[127],"facilitated":[130],"proteasomal":[132],"degradation":[133],"while":[136,157],"inducing":[137],"NDRG1":[140,146],"(N-myc":[141],"downstream":[142],"regulated":[143],"1":[144],"gene).":[145],"enhanced":[147],"interaction":[149],"ubiquitin":[154],"ligase":[155],"NEDD4,":[156],"PYK2,":[158],"interacts":[160],"NEDD4":[162],"HER3,":[164],"interfered":[165],"NEDD4\u2013HER3":[167],"binding,":[168],"suggesting":[169],"PYK2\u2013NDRG1\u2013NEDD4":[172],"circuit":[173],"has":[174],"critical":[176],"role":[177],"receptor":[179],"degradation,":[180],"response,":[182],"resistance":[184],"mechanism.":[185],"Our":[186],"studies":[187],"offer":[188],"preclinical":[190],"proof":[191],"concept":[193],"for":[194],"strategy":[196],"cotargeting":[198],"improve":[205],"therapy.":[207],"Cancer":[208],"Res;":[209],"77(1);":[210],"86\u201399.":[211],"\u00a92016":[212],"AACR.":[213]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2023-04-05T00:00:00"}