{"id":"https://openalex.org/W4220876249","doi":"https://doi.org/10.1073/pnas.2120403119","title":"Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway","display_name":"Sensitivity of VHL mutant kidney cancers to HIF2 inhibitors does not require an intact p53 pathway","publication_year":2022,"publication_date":"2022-03-31","ids":{"openalex":"https://openalex.org/W4220876249","doi":"https://doi.org/10.1073/pnas.2120403119","pmid":"https://pubmed.ncbi.nlm.nih.gov/35357972"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.2120403119","doi":"https://doi.org/10.1073/pnas.2120403119","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.2120403119","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://doi.org/10.1073/pnas.2120403119","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5022314654","display_name":"Laura A. Stransky","orcid":"https://orcid.org/0000-0001-8834-936X","observed_orcids":["https://orcid.org/0000-0001-8834-936X"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Laura A. Stransky","raw_affiliation_strings":["Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215"],"raw_orcid":"https://orcid.org/0000-0001-8834-936X","affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5052892170","display_name":"Sean M. Vigeant","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sean M. Vigeant","raw_affiliation_strings":["Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5006671672","display_name":"Bofu Huang","orcid":"https://orcid.org/0000-0001-5855-2180","observed_orcids":["https://orcid.org/0000-0001-5855-2180"]},"institutions":[{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Bofu Huang","raw_affiliation_strings":["Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210117453"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5081239309","display_name":"Destiny J. West","orcid":"https://orcid.org/0009-0004-5960-5271","observed_orcids":["https://orcid.org/0009-0004-5960-5271"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Destiny West","raw_affiliation_strings":["Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025893013","display_name":"Thomas Denize","orcid":"https://orcid.org/0000-0002-8618-7691","observed_orcids":["https://orcid.org/0000-0002-8618-7691"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Thomas Denize","raw_affiliation_strings":["Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"],"raw_orcid":"https://orcid.org/0000-0002-8618-7691","affiliations":[{"raw_affiliation_string":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062503540","display_name":"Emily Walton","orcid":"https://orcid.org/0000-0003-2117-5988","observed_orcids":["https://orcid.org/0000-0003-2117-5988"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Emily Walton","raw_affiliation_strings":["Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046795494","display_name":"Sabina Signoretti","orcid":"https://orcid.org/0000-0002-5000-9105","observed_orcids":["https://orcid.org/0000-0002-5000-9105"]},"institutions":[{"id":"https://openalex.org/I1283280774","display_name":"Brigham and Women's Hospital","ror":"https://ror.org/04b6nzv94","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I121934306","https://openalex.org/I1283280774","https://openalex.org/I48633490"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Sabina Signoretti","raw_affiliation_strings":["Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Pathology, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, MA 02115","institution_ids":["https://openalex.org/I1283280774","https://openalex.org/I136199984"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5088456751","display_name":"William G. Kaelin","orcid":"https://orcid.org/0000-0002-0574-4856","observed_orcids":["https://orcid.org/0000-0002-0574-4856"]},"institutions":[{"id":"https://openalex.org/I1344073410","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90","country_code":"US","type":"facility","lineage":["https://openalex.org/I1344073410"]},{"id":"https://openalex.org/I136199984","display_name":"Harvard University","ror":"https://ror.org/03vek6s52","country_code":"US","type":"education","lineage":["https://openalex.org/I136199984"]},{"id":"https://openalex.org/I4210117453","display_name":"Dana-Farber Cancer Institute","ror":"https://ror.org/02jzgtq86","country_code":"US","type":"facility","lineage":["https://openalex.org/I4210117453"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"William G. Kaelin","raw_affiliation_strings":["Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215","HHMI, Chevy Chase, MD 20815"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Dana\u2013Farber Cancer Institute, Harvard Medical School, Boston, MA 02215","institution_ids":["https://openalex.org/I136199984","https://openalex.org/I4210117453"]},{"raw_affiliation_string":"HHMI, Chevy Chase, MD 20815","institution_ids":["https://openalex.org/I1344073410"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":4,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":2.3464,"has_fulltext":false,"cited_by_count":35,"citation_normalized_percentile":{"value":0.90860993,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":93,"max":99},"biblio":{"volume":"119","issue":"14","first_page":"e2120403119","last_page":"e2120403119"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.7832000255584717,"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"}},"topics":[{"id":"https://openalex.org/T10631","display_name":"Cancer, Hypoxia, and Metabolism","score":0.7832000255584717,"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/T10449","display_name":"Renal cell carcinoma treatment","score":0.2011999934911728,"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/T11297","display_name":"Ferroptosis and cancer prognosis","score":0.0017000000225380063,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/vhl-tumor-suppressor-gene","display_name":"VHL tumor suppressor","score":0.843999981880188},{"id":"https://openalex.org/keywords/clear-cell-renal-cell-carcinoma","display_name":"clear cell renal cell carcinoma","score":0.9800000190734863},{"id":"https://openalex.org/keywords/belzutifan","display_name":"belzutifan","score":0.9800000190734863},{"id":"https://openalex.org/keywords/p53-signaling-pathway","display_name":"p53 pathway","score":0.8489999771118164},{"id":"https://openalex.org/keywords/drug-sensitivity","display_name":"drug sensitivity","score":0.5149999856948853},{"id":"https://openalex.org/keywords/von-hippel-lindau-disease","display_name":"von Hippel-Lindau disease","score":0.6589999794960022},{"id":"https://openalex.org/keywords/hypoxia-inducible-factor","display_name":"hypoxia-inducible factor","score":0.7419999837875366},{"id":"https://openalex.org/keywords/biomarker-prediction","display_name":"biomarker prediction","score":0.4359999895095825},{"id":"https://openalex.org/keywords/crispr-cas9-genome-editing","display_name":"CRISPR/Cas9 genome editing","score":0.6769999861717224}],"concepts":[{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.7036455273628235},{"id":"https://openalex.org/C2781278892","wikidata":"https://www.wikidata.org/wiki/Q18556340","display_name":"Clear cell renal cell carcinoma","level":3,"score":0.6228743195533752},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5691518783569336},{"id":"https://openalex.org/C2778264664","wikidata":"https://www.wikidata.org/wiki/Q422445","display_name":"Tumor suppressor gene","level":4,"score":0.478725403547287},{"id":"https://openalex.org/C160450060","wikidata":"https://www.wikidata.org/wiki/Q104598479","display_name":"Hypoxia-inducible factors","level":3,"score":0.45541006326675415},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4096423387527466},{"id":"https://openalex.org/C555283112","wikidata":"https://www.wikidata.org/wiki/Q1637543","display_name":"Carcinogenesis","level":3,"score":0.2748395800590515},{"id":"https://openalex.org/C2777472916","wikidata":"https://www.wikidata.org/wiki/Q1164529","display_name":"Renal cell carcinoma","level":2,"score":0.2517228126525879},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2089928388595581},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1872943639755249},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.18249481916427612},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.1385686695575714}],"mesh":[{"descriptor_ui":"D000099162","descriptor_name":"Endothelial PAS Domain-Containing Protein 1","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D002292","descriptor_name":"Carcinoma, Renal Cell","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D007189","descriptor_name":"Indans","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D007680","descriptor_name":"Kidney Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008297","descriptor_name":"Male","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":true},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D013450","descriptor_name":"Sulfones","qualifier_ui":"Q000627","qualifier_name":"therapeutic use","is_major_topic":true},{"descriptor_ui":"D015972","descriptor_name":"Gene Expression Regulation, Neoplastic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015972","descriptor_name":"Gene Expression Regulation, Neoplastic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015972","descriptor_name":"Gene Expression Regulation, Neoplastic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D016159","descriptor_name":"Tumor Suppressor Protein p53","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D045744","descriptor_name":"Cell Line, Tumor","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Proteins","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000037","qualifier_name":"antagonists & inhibitors","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Proteins","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Proteins","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D051792","descriptor_name":"Basic Helix-Loop-Helix Transcription Factors","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D051794","descriptor_name":"Von Hippel-Lindau Tumor Suppressor Protein","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1073/pnas.2120403119","doi":"https://doi.org/10.1073/pnas.2120403119","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.2120403119","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmid:35357972","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/35357972","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":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Journal Article"},{"id":"pmh:oai:pubmedcentral.nih.gov:9168943","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9168943","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Proc Natl Acad Sci U S A","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1073/pnas.2120403119","doi":"https://doi.org/10.1073/pnas.2120403119","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.2120403119","pdf_url":null,"source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.98580002784729}],"sustainable_development_goals_aurora":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.7900000214576721}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1273380608","display_name":null,"funder_award_id":"P50CA101942","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G3103019320","display_name":null,"funder_award_id":"R35CA100068","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G4561983161","display_name":null,"funder_award_id":"P30 CA006516","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G6155655953","display_name":null,"funder_award_id":"P50-CA101942-12","funder_id":"https://openalex.org/F4320310274","funder_display_name":"Dana-Farber/Harvard Cancer Center"},{"id":"https://openalex.org/G6619816607","display_name":null,"funder_award_id":"T32 CA236754","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000864353","display_name":"The von Hippel-Lindau Tumor Suppressor Gene and Kidney Cancer: Insights into Oxygen Sensing and Treating Cancers Caused by Undruggable Mutations","funder_award_id":"R35CA210068","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"},{"id":"https://openalex.org/G9000882983","display_name":"Developing a Translation Pipeline for VHL Mutant Malignancies","funder_award_id":"U01CA236489","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320306082","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90"},{"id":"https://openalex.org/F4320310274","display_name":"Dana-Farber/Harvard Cancer Center","ror":"https://ror.org/03pvyf116"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":46,"referenced_works":["https://openalex.org/W1968657935","https://openalex.org/W1980522580","https://openalex.org/W1990607537","https://openalex.org/W1998664010","https://openalex.org/W2009520390","https://openalex.org/W2015644147","https://openalex.org/W2020344223","https://openalex.org/W2042702043","https://openalex.org/W2058141882","https://openalex.org/W2058893130","https://openalex.org/W2071361463","https://openalex.org/W2073731809","https://openalex.org/W2081460564","https://openalex.org/W2094242056","https://openalex.org/W2095698093","https://openalex.org/W2096172976","https://openalex.org/W2129621205","https://openalex.org/W2134212067","https://openalex.org/W2136109165","https://openalex.org/W2159368804","https://openalex.org/W2161609794","https://openalex.org/W2164210517","https://openalex.org/W2167279371","https://openalex.org/W2167845320","https://openalex.org/W2335012284","https://openalex.org/W2469401140","https://openalex.org/W2510079645","https://openalex.org/W2513249090","https://openalex.org/W2514212469","https://openalex.org/W2580449060","https://openalex.org/W2620006923","https://openalex.org/W2765829307","https://openalex.org/W2778771081","https://openalex.org/W2782183686","https://openalex.org/W2796207353","https://openalex.org/W2797542577","https://openalex.org/W2800869096","https://openalex.org/W2801027227","https://openalex.org/W2921405643","https://openalex.org/W2955214382","https://openalex.org/W2979284331","https://openalex.org/W2986293512","https://openalex.org/W3089803871","https://openalex.org/W3154810465","https://openalex.org/W3215948599","https://openalex.org/W4294358748"],"related_works":["https://openalex.org/W3130606105","https://openalex.org/W4387606434","https://openalex.org/W3012319723","https://openalex.org/W2768024453","https://openalex.org/W4232921416","https://openalex.org/W4313645088","https://openalex.org/W3091590753","https://openalex.org/W4220968584","https://openalex.org/W2947044050","https://openalex.org/W1973332845"],"abstract_inverted_index":{"Inactivation":[0],"of":[1,25,50,138],"the":[2,8,21,170],"VHL":[3,29,56,86,93],"tumor":[4,30,53,57],"suppressor":[5,31,58],"gene":[6],"is":[7,20,45,78,89,175,200],"signature":[9],"initiating":[10],"event":[11],"in":[12,83,100,116,148,195],"clear":[13],"cell":[14,16,140],"renal":[15],"carcinoma":[17],"(ccRCC),":[18],"which":[19,88,174,209],"most":[22],"common":[23],"form":[24],"kidney":[26],"cancer.":[27],"The":[28,47],"protein":[32,59],"marks":[33],"hypoxia-inducible":[34],"factor":[35],"1":[36],"(HIF1)":[37],"and":[38,77,103,131,158,198],"HIF2":[39,51,66,95,124,129,165,171,191,215],"for":[40,74,80,123,207],"proteasomal":[41],"degradation":[42],"when":[43],"oxygen":[44],"present.":[46],"inappropriate":[48],"accumulation":[49],"drives":[52],"formation":[54],"by":[55,91,114],"(pVHL)\u2013defective":[60],"ccRCC.":[61],"Belzutifan,":[62],"a":[63,135,204],"first-in-class":[64],"allosteric":[65],"inhibitor,":[67],"has":[68],"advanced":[69,75],"to":[70,118,164,178,202,214],"phase":[71],"3":[72],"testing":[73],"ccRCC":[76,139,149,210],"approved":[79],"ccRCCs":[81],"arising":[82],"patients":[84,211],"with":[85],"disease,":[87],"caused":[90],"germline":[92],"mutations.":[94],"can":[96],"suppress":[97],"p53":[98,110,132,146,186],"function":[99,147],"some":[101],"settings":[102],"preliminary":[104],"data":[105],"suggested":[106],"that":[107,151,185],"an":[108],"intact":[109],"pathway,":[111],"as":[112],"measured":[113],"activation":[115],"response":[117],"DNA":[119],"damage,":[120],"was":[121],"necessary":[122],"dependence.":[125],"Here,":[126],"we":[127,183],"correlated":[128],"dependence":[130],"status":[133,187],"across":[134],"broader":[136],"collection":[137],"lines.":[141],"We":[142],"also":[143],"genetically":[144],"manipulated":[145],"lines":[150],"were":[152,154],"or":[153,169],"not":[155,189],"previously":[156],"HIF2-dependent":[157],"then":[159],"assessed":[160],"their":[161],"subsequent":[162],"sensitivity":[163],"ablation":[166],"using":[167],"CRISPR-Cas9":[168],"inhibitor":[172],"PT2399,":[173],"closely":[176],"related":[177],"belzutifan.":[179],"From":[180],"these":[181],"studies,":[182],"conclude":[184],"does":[188],"dictate":[190],"dependence,":[192],"at":[193],"least":[194],"preclinical":[196],"models,":[197],"thus":[199],"unlikely":[201],"be":[203],"useful":[205],"biomarker":[206],"predicting":[208],"will":[212],"respond":[213],"inhibitors.":[216]},"counts_by_year":[{"year":2026,"cited_by_count":7},{"year":2025,"cited_by_count":9},{"year":2024,"cited_by_count":10},{"year":2023,"cited_by_count":2},{"year":2022,"cited_by_count":7}],"updated_date":"2026-10-15T10:00:46.086208","created_date":"2022-04-03T00:00:00"}