{"id":"https://openalex.org/W4256316672","doi":"https://doi.org/10.1634/theoncologist.1-4-223","title":"Resistance Mechanisms to Methotrexate in Tumors","display_name":"Resistance Mechanisms to Methotrexate in Tumors","publication_year":1996,"publication_date":"1996-08-01","ids":{"openalex":"https://openalex.org/W4256316672","doi":"https://doi.org/10.1634/theoncologist.1-4-223"},"language":"en","primary_location":{"id":"doi:10.1634/theoncologist.1-4-223","doi":"https://doi.org/10.1634/theoncologist.1-4-223","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.1-4-223","pdf_url":"https://academic.oup.com/oncolo/article-pdf/1/4/223/41831116/oncolo_1_4_223.pdf","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://academic.oup.com/oncolo/article-pdf/1/4/223/41831116/oncolo_1_4_223.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5104110678","display_name":"Joseph R. Bertino","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"J.R. Bertino","raw_affiliation_strings":["Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5062647247","display_name":"Erdem G\u00f6ker","orcid":"https://orcid.org/0000-0001-6180-713X","observed_orcids":["https://orcid.org/0000-0001-6180-713X"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"E. G\u00f6ker","raw_affiliation_strings":["Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5032743242","display_name":"Richard Greg Gorlick","orcid":"https://orcid.org/0000-0001-8995-2929","observed_orcids":["https://orcid.org/0000-0001-8995-2929"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"R. Gorlick","raw_affiliation_strings":["Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5012770514","display_name":"W. W. Li","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"W.W. Li","raw_affiliation_strings":["Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA","institution_ids":["https://openalex.org/I1334819555"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5064988009","display_name":"Debabrata Banerjee","orcid":"https://orcid.org/0000-0001-7794-7831","observed_orcids":["https://orcid.org/0000-0001-7794-7831"]},"institutions":[{"id":"https://openalex.org/I1334819555","display_name":"Memorial Sloan Kettering Cancer Center","ror":"https://ror.org/02yrq0923","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1334819555"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"D. Banerjee","raw_affiliation_strings":["Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA","institution_ids":["https://openalex.org/I1334819555"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5104110678"],"corresponding_institution_ids":["https://openalex.org/I1334819555"],"apc_list":{"value":3852,"currency":"USD","value_usd":3852},"apc_paid":null,"fwci":0.0,"has_fulltext":true,"cited_by_count":49,"citation_normalized_percentile":{"value":0.42556321,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":99},"biblio":{"volume":"1","issue":"4","first_page":"223","last_page":"226"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9794999957084656,"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/T10570","display_name":"Drug Transport and Resistance Mechanisms","score":0.9794999957084656,"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/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.007799999788403511,"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/T10583","display_name":"Cancer-related Molecular Pathways","score":0.0010000000474974513,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/methotrexate-resistance","display_name":"methotrexate resistance","score":0.9700000286102295},{"id":"https://openalex.org/keywords/dihydrofolate-reductase","display_name":"dihydrofolate reductase","score":0.8610000014305115},{"id":"https://openalex.org/keywords/acute-lymphoblastic-leukemia","display_name":"acute lymphoblastic leukemia","score":0.796999990940094},{"id":"https://openalex.org/keywords/acute-myeloid-leukemia","display_name":"acute myeloid leukemia","score":0.9589999914169312},{"id":"https://openalex.org/keywords/soft-tissue-sarcoma","display_name":"soft tissue sarcoma","score":0.9990000128746033},{"id":"https://openalex.org/keywords/drug-uptake","display_name":"drug uptake","score":0.656000018119812},{"id":"https://openalex.org/keywords/polyglutamylation","display_name":"polyglutamylation","score":0.9160000085830688},{"id":"https://openalex.org/keywords/retinoblastoma-protein","display_name":"retinoblastoma protein","score":0.9599999785423279},{"id":"https://openalex.org/keywords/e2f-transcription-factors","display_name":"E2F transcription factors","score":0.8989999890327454},{"id":"https://openalex.org/keywords/drug-survival","display_name":"drug retention","score":0.5149999856948853},{"id":"https://openalex.org/keywords/antifolate-drugs","display_name":"antifolate","score":0.5249999761581421}],"concepts":[{"id":"https://openalex.org/C2781059491","wikidata":"https://www.wikidata.org/wiki/Q422232","display_name":"Methotrexate","level":2,"score":0.7865621447563171},{"id":"https://openalex.org/C2776577112","wikidata":"https://www.wikidata.org/wiki/Q500695","display_name":"Retinoblastoma","level":3,"score":0.7581000328063965},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7419604063034058},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6831138134002686},{"id":"https://openalex.org/C2781320022","wikidata":"https://www.wikidata.org/wiki/Q417149","display_name":"Dihydrofolate reductase","level":3,"score":0.629144012928009},{"id":"https://openalex.org/C2776062698","wikidata":"https://www.wikidata.org/wiki/Q21111463","display_name":"Retinoblastoma protein","level":4,"score":0.5674158334732056},{"id":"https://openalex.org/C114851261","wikidata":"https://www.wikidata.org/wiki/Q12147416","display_name":"Drug resistance","level":2,"score":0.5516176223754883},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.5428441166877747},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.42876261472702026},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.37038683891296387},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.31227046251296997},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.2930489182472229},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.28313153982162476},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.2753009498119354},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.19490402936935425},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.16338467597961426},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.12541010975837708},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.1099090576171875}],"mesh":[],"locations_count":2,"locations":[{"id":"doi:10.1634/theoncologist.1-4-223","doi":"https://doi.org/10.1634/theoncologist.1-4-223","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.1-4-223","pdf_url":"https://academic.oup.com/oncolo/article-pdf/1/4/223/41831116/oncolo_1_4_223.pdf","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},{"id":"pmh:oai:alma.01RUT_INST:11665003930004646","doi":null,"is_oa":false,"landing_page_url":"https://scholarship.libraries.rutgers.edu/esploro/outputs/journalArticle/Resistance-Mechanisms-to-Methotrexate-in-Tumors/991031665852204646","pdf_url":null,"source":{"id":"https://openalex.org/S4306401388","display_name":"Rutgers University Community Repository (Rutgers University)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I102322142","host_organization_name":"Rutgers, The State University of New Jersey","host_organization_lineage":["https://openalex.org/I102322142"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"text"}],"best_oa_location":{"id":"doi:10.1634/theoncologist.1-4-223","doi":"https://doi.org/10.1634/theoncologist.1-4-223","is_oa":true,"landing_page_url":"https://doi.org/10.1634/theoncologist.1-4-223","pdf_url":"https://academic.oup.com/oncolo/article-pdf/1/4/223/41831116/oncolo_1_4_223.pdf","source":{"id":"https://openalex.org/S15523509","display_name":"The Oncologist","issn_l":"1083-7159","issn":["1083-7159","1549-490X"],"is_oa":false,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-c","doyens","jufo-1","ki-jl-1","medline","norway-1","oarl","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310316295","host_organization_name":"AlphaMed Press","host_organization_lineage":["https://openalex.org/P4310316295"],"host_organization_lineage_names":["AlphaMed Press"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"The Oncologist","raw_type":"journal-article"},"sustainable_development_goals":[{"score":0.9537000060081482,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2943714584","display_name":null,"funder_award_id":"#DHP-18K","funder_id":"https://openalex.org/F4320306095","funder_display_name":"American Cancer Society"},{"id":"https://openalex.org/G4733012208","display_name":null,"funder_award_id":"47179","funder_id":"https://openalex.org/F4320332505","funder_display_name":"U.S. Public Health Service"},{"id":"https://openalex.org/G8254997467","display_name":null,"funder_award_id":"PO1-CA-47179","funder_id":"https://openalex.org/F4320306095","funder_display_name":"American Cancer Society"}],"funders":[{"id":"https://openalex.org/F4320306095","display_name":"American Cancer Society","ror":"https://ror.org/02e463172"},{"id":"https://openalex.org/F4320332505","display_name":"U.S. Public Health Service","ror":"https://ror.org/05xf94514"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W4256316672.pdf","grobid_xml":"https://content.openalex.org/works/W4256316672.grobid-xml"},"referenced_works_count":20,"referenced_works":["https://openalex.org/W37509717","https://openalex.org/W68159151","https://openalex.org/W284120598","https://openalex.org/W584609198","https://openalex.org/W1485133218","https://openalex.org/W1529220262","https://openalex.org/W1589005530","https://openalex.org/W1804726264","https://openalex.org/W1818833536","https://openalex.org/W1965250903","https://openalex.org/W1970726343","https://openalex.org/W2036095352","https://openalex.org/W2079384901","https://openalex.org/W2094028578","https://openalex.org/W2106612113","https://openalex.org/W2108172661","https://openalex.org/W2271920406","https://openalex.org/W2328999771","https://openalex.org/W2340061261","https://openalex.org/W2434422421"],"related_works":["https://openalex.org/W2017953852","https://openalex.org/W1982020575","https://openalex.org/W2054954475","https://openalex.org/W3030853942","https://openalex.org/W2091068832","https://openalex.org/W2413325248","https://openalex.org/W2309790127","https://openalex.org/W34293985","https://openalex.org/W1980524534","https://openalex.org/W2397703940"],"abstract_inverted_index":{"Abstract":[0],"The":[1],"mechanisms":[2,26],"of":[3,40,60,68,75,101,103,112],"intrinsic":[4,41,80],"and":[5,31,50,79],"acquired":[6],"resistance":[7,25,42,82],"to":[8,43,56,65,90,97],"methotrexate":[9],"(MTX)":[10],"in":[11,45,51,93,110],"human":[12],"tumors":[13],"are":[14,28],"reviewed":[15],"herein.":[16],"In":[17],"blasts":[18],"from":[19],"patients":[20],"with":[21],"acute":[22,52],"lymphocytic":[23],"leukemia,":[24],"found":[27],"decreased":[29],"uptake":[30],"increased":[32,99],"dihydrofolate":[33],"reductase":[34],"(DHFR)":[35],"activity.":[36],"A":[37,70],"major":[38],"cause":[39],"MTX":[44,81],"soft":[46],"tissue":[47],"sarcoma":[48],"cells":[49],"myelocytic":[53],"leukemia":[54],"appears":[55],"be":[57],"a":[58],"lack":[59,74],"drug":[61],"retention,":[62],"due":[63,96],"mainly":[64],"low":[66],"levels":[67,111],"polyglutamylation.":[69],"novel":[71],"association":[72],"between":[73],"the":[76],"retinoblastoma":[77,119],"protein":[78],"has":[83,87],"been":[84,88],"found.":[85],"This":[86],"attributed":[89],"an":[91,98,108],"increase":[92,109],"DHFR":[94],"activity,":[95],"rate":[100],"transcription":[102],"this":[104],"gene,":[105],"stimulated":[106],"by":[107,117],"free":[113],"E2F,":[114],"not":[115],"sequestered":[116],"hypophosphorylated":[118],"protein.":[120]},"counts_by_year":[{"year":2025,"cited_by_count":1},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":5},{"year":2020,"cited_by_count":9},{"year":2019,"cited_by_count":8},{"year":2018,"cited_by_count":3},{"year":2017,"cited_by_count":7},{"year":2016,"cited_by_count":6},{"year":2015,"cited_by_count":1},{"year":2013,"cited_by_count":2},{"year":2012,"cited_by_count":1}],"updated_date":"2026-10-08T09:06:37.294493","created_date":"2022-05-12T00:00:00"}