{"id":"https://openalex.org/W7205016266","doi":"https://doi.org/10.1158/1535-7163.c.8688039","title":"Data from MRTX1133 Suppresses ERK Signaling but Elicits Context-Dependent Antiproliferative Responses in KRAS (G12C) Cancer Cells","display_name":"Data from MRTX1133 Suppresses ERK Signaling but Elicits Context-Dependent Antiproliferative Responses in KRAS (G12C) Cancer Cells","publication_year":2026,"publication_date":"2026-09-02","ids":{"openalex":"https://openalex.org/W7205016266","doi":"https://doi.org/10.1158/1535-7163.c.8688039"},"language":"en","primary_location":{"id":"doi:10.1158/1535-7163.c.8688039","doi":"https://doi.org/10.1158/1535-7163.c.8688039","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.8688039","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"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.8688039","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5063000558","display_name":"Abraham C. Sianoya","orcid":"https://orcid.org/0000-0002-5070-7843","observed_orcids":["https://orcid.org/0000-0002-5070-7843"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Abraham C. Sianoya","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-5070-7843","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5149038319","display_name":"Yan Zuo","orcid":"https://orcid.org/0009-0008-2555-2756","observed_orcids":["https://orcid.org/0009-0008-2555-2756"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Yan Zuo","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0008-2555-2756","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061390911","display_name":"Cynthia V. Pagba","orcid":"https://orcid.org/0000-0002-3642-4361","observed_orcids":["https://orcid.org/0000-0002-3642-4361"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cynthia V. Pagba","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-3642-4361","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5089666266","display_name":"Jacob L. Jakubec","orcid":"https://orcid.org/0009-0007-2017-8497","observed_orcids":["https://orcid.org/0009-0007-2017-8497"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jacob L. Jakubec","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0007-2017-8497","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5041724011","display_name":"Stephanie A. Planque","orcid":"https://orcid.org/0009-0009-0057-3603","observed_orcids":["https://orcid.org/0009-0009-0057-3603"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Stephanie A. Planque","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0009-0009-0057-3603","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046674705","display_name":"Jeffrey A. Frost","orcid":"https://orcid.org/0000-0001-9722-1536","observed_orcids":["https://orcid.org/0000-0001-9722-1536"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jeffrey A. Frost","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-9722-1536","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011332945","display_name":"Paul Mark B. Medina","orcid":"https://orcid.org/0000-0001-6116-1818","observed_orcids":["https://orcid.org/0000-0001-6116-1818"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paul Mark B. Medina","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0001-6116-1818","affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5087588530","display_name":"Alemayehu Abebe Gorfe","orcid":"https://orcid.org/0000-0002-9328-4692","observed_orcids":["https://orcid.org/0000-0002-9328-4692"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alemayehu A. Gorfe","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-9328-4692","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/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.9502000212669373,"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"}},"topics":[{"id":"https://openalex.org/T10169","display_name":"Protein Kinase Regulation and GTPase Signaling","score":0.9502000212669373,"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/T11533","display_name":"Melanoma and MAPK Pathways","score":0.024800000712275505,"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/T12104","display_name":"Protein Tyrosine Phosphatases","score":0.007699999958276749,"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/mrtx1133","display_name":"MRTX1133","score":0.9990000128746033},{"id":"https://openalex.org/keywords/kras-g12c","display_name":"KRAS G12C","score":0.9010000228881836},{"id":"https://openalex.org/keywords/kras-g12d","display_name":"KRAS G12D","score":0.7929999828338623},{"id":"https://openalex.org/keywords/erk-signaling","display_name":"ERK signaling","score":0.8659999966621399},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.972000002861023},{"id":"https://openalex.org/keywords/nucleotide-exchange","display_name":"nucleotide exchange","score":0.8370000123977661},{"id":"https://openalex.org/keywords/ribosomal-protein-s6","display_name":"ribosomal protein S6","score":0.8529999852180481},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.8799999952316284},{"id":"https://openalex.org/keywords/mia-paca-2-cells","display_name":"MIA PaCa-2 cells","score":0.7900000214576721},{"id":"https://openalex.org/keywords/tumor-growth","display_name":"tumor growth","score":0.4339999854564667},{"id":"https://openalex.org/keywords/chemical-probes","display_name":"chemical probes","score":0.6779999732971191},{"id":"https://openalex.org/keywords/sotorasib","display_name":"sotorasib","score":0.7609999775886536},{"id":"https://openalex.org/keywords/adagrasib","display_name":"adagrasib","score":0.9819999933242798}],"concepts":[{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.9854000210762024},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6935999989509583},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.6166999936103821},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.5875999927520752},{"id":"https://openalex.org/C51785407","wikidata":"https://www.wikidata.org/wiki/Q2627568","display_name":"Effector","level":2,"score":0.5547999739646912},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.5052000284194946},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.49799999594688416},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.4731999933719635},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.4643000066280365},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.39559999108314514},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.37610000371932983},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.3596000075340271},{"id":"https://openalex.org/C535046627","wikidata":"https://www.wikidata.org/wiki/Q30612","display_name":"Clinical trial","level":2,"score":0.35409998893737793},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.3490000069141388},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.34549999237060547},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.3449000120162964},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3190999925136566},{"id":"https://openalex.org/C2776087337","wikidata":"https://www.wikidata.org/wiki/Q7448840","display_name":"Selumetinib","level":5,"score":0.3131999969482422},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.30250000953674316},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.29190000891685486},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.26269999146461487},{"id":"https://openalex.org/C2994372470","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell lines","level":4,"score":0.2621999979019165},{"id":"https://openalex.org/C143065580","wikidata":"https://www.wikidata.org/wiki/Q3285695","display_name":"Mutant","level":3,"score":0.2583000063896179}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1535-7163.c.8688039","doi":"https://doi.org/10.1158/1535-7163.c.8688039","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.8688039","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"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.8688039","doi":"https://doi.org/10.1158/1535-7163.c.8688039","is_oa":true,"landing_page_url":"https://doi.org/10.1158/1535-7163.c.8688039","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"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/W7135403100","https://openalex.org/W4304084008","https://openalex.org/W7205003435","https://openalex.org/W4403550977","https://openalex.org/W4307034052","https://openalex.org/W7148741003","https://openalex.org/W4362545683","https://openalex.org/W4282939955","https://openalex.org/W3023464827","https://openalex.org/W4389239923"],"abstract_inverted_index":{"Abstract":[0],"KRAS":[1,54,83,98,108,116,132,141,194,227,248],"is":[2,91,145],"a":[3,20,53,86,92,188,238],"high-value":[4],"therapeutic":[5],"target":[6,19],"for":[7,30,75,94,205],"the":[8,39,59,67,107,138,150,153,163,198,203,233],"treatment":[9],"of":[10,34,41,62,70,97,140,152,166,190,222,235],"cancer.":[11],"Two":[12],"covalent":[13],"inhibitors,":[14],"sotorasib":[15,63],"and":[16,66,88,120,124,178,250],"adagrasib,":[17],"which":[18],"specific":[21],"codon":[22],"12":[23],"mutation":[24],"(G12C),":[25],"had":[26,48],"received":[27],"accelerated":[28],"approvals":[29],"clinical":[31,50,73],"use.":[32],"Studies":[33],"these":[35],"inhibitors":[36,43,84],"ushered":[37],"in":[38,127,176],"development":[40],"new":[42],"such":[44,196],"as":[45,52,64,160,162,197,237],"MRTX1133":[46,76,110,147,223,236],"that":[47,78,89,106,207,241],"entered":[49],"trials":[51],"(G12D)-selective,":[55],"noncovalent":[56],"inhibitor.":[57],"However,":[58,134],"subsequent":[60],"failure":[61],"monotherapy":[65],"recent":[68,217],"termination":[69],"an":[71],"early-phase":[72],"trial":[74],"indicate":[77],"developing":[79],"clinically":[80],"effective":[81],"allele-specific":[82],"remains":[85],"challenge":[87],"there":[90],"need":[93,204],"further":[95,231],"evaluation":[96],"inhibition":[99,251],"mechanisms.":[100,252],"In":[101],"this":[102],"study,":[103],"we":[104],"show":[105],"(G12D)-selective":[109],"also":[111],"binds":[112],"to":[113,184,187,224,243],"G12C":[114],"mutant":[115],"with":[117,215],"high":[118],"affinity":[119],"suppresses":[121],"nucleotide":[122],"exchange":[123],"MAPK":[125],"signaling":[126],"cancer":[128,143,155,180],"cell":[129,156],"lines":[130],"harboring":[131],"(G12C).":[133],"its":[135],"effect":[136,191],"on":[137,192,219,247],"proliferation":[139,151],"(G12C)":[142],"cells":[144],"context-dependent;":[146],"robustly":[148],"inhibits":[149],"pancreatic":[154],"line":[157],"MIA":[158,167],"PaCa-2":[159,168],"well":[161],"tumor":[164],"growth":[165],"mouse":[169],"xenografts,":[170],"whereas":[171],"it":[172],"has":[173],"minimal":[174],"effects":[175],"lung":[177],"colorectal":[179],"cells.":[181],"This":[182],"seems":[183],"be":[185],"due":[186],"lack":[189],"downstream":[193],"effectors":[195],"ribosomal":[199],"protein":[200],"S6,":[201],"highlighting":[202],"strategies":[206],"take":[208],"into":[209],"account":[210],"potential":[211],"context-dependent":[212],"processes.":[213],"Together":[214],"other":[216,225],"reports":[218],"high-affinity":[220],"binding":[221],"non-G12D":[226],"mutants,":[228],"our":[229],"findings":[230],"reveal":[232],"usefulness":[234],"chemical":[239],"probe":[240],"continues":[242],"provide":[244],"novel":[245],"insights":[246],"biology":[249]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-09-02T00:00:00"}