{"id":"https://openalex.org/W7214101461","doi":"https://doi.org/10.17863/cam.134595","title":"Pharmacological inhibition of METTL1 as a therapy against solid and haematological cancers","display_name":"Pharmacological inhibition of METTL1 as a therapy against solid and haematological cancers","publication_year":2026,"publication_date":"2026-09-22","ids":{"openalex":"https://openalex.org/W7214101461","doi":"https://doi.org/10.17863/cam.134595"},"language":"en","primary_location":{"id":"pmh:oai:www.repository.cam.ac.uk:1810/408445","doi":null,"is_oa":true,"landing_page_url":"https://www.repository.cam.ac.uk/handle/1810/408445","pdf_url":null,"source":{"id":"https://openalex.org/S4306401777","display_name":"Apollo (University of Cambridge)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I241749","host_organization_name":"University of Cambridge","host_organization_lineage":["https://openalex.org/I241749"],"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":null,"raw_type":"Article"},"volume":null,"type":"article","indexed_in":["datacite"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.repository.cam.ac.uk/handle/1810/408445","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5002638060","display_name":"Konstantinos Tzelepis","orcid":"https://orcid.org/0000-0002-4865-7648","observed_orcids":["https://orcid.org/0000-0002-4865-7648"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Tzelepis, Kostas","raw_affiliation_strings":[],"raw_orcid":"https://orcid.org/0000-0002-4865-7648","affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086755030","display_name":"Elisa Laurenti","orcid":"https://orcid.org/0000-0002-9917-9092","observed_orcids":["https://orcid.org/0000-0002-9917-9092"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Laurenti, Elisa","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049770229","display_name":"Walid T. Khaled","orcid":"https://orcid.org/0000-0001-9068-5776","observed_orcids":["https://orcid.org/0000-0001-9068-5776"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Khaled, Walid","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5005571428","display_name":"Fotios Sampaziotis","orcid":"https://orcid.org/0000-0003-0812-7586","observed_orcids":["https://orcid.org/0000-0003-0812-7586"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sampaziotis, Fotios","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5152575799","display_name":"Alcolea","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alcolea","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5152538572","display_name":"George Vassiliou","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vassiliou, George","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5029251605","display_name":"Brian J.P. Huntly","orcid":"https://orcid.org/0000-0003-0312-161X","observed_orcids":["https://orcid.org/0000-0003-0312-161X"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Huntly, Brian","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":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.67441822,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"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/T11482","display_name":"RNA modifications and cancer","score":1.0,"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/T11482","display_name":"RNA modifications and cancer","score":1.0,"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/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.0,"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/T13157","display_name":"Cancer-related gene regulation","score":0.0,"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/mettl1","display_name":"METTL1","score":0.9670000076293945},{"id":"https://openalex.org/keywords/trna-methylation","display_name":"tRNA methylation","score":0.6650000214576721},{"id":"https://openalex.org/keywords/7-methylguanosine","display_name":"7-methylguanosine","score":0.9559999704360962},{"id":"https://openalex.org/keywords/wdr4","display_name":"WDR4","score":0.7540000081062317},{"id":"https://openalex.org/keywords/cancer-therapy","display_name":"cancer therapy","score":0.6660000085830688},{"id":"https://openalex.org/keywords/leukemia","display_name":"leukemia","score":0.8370000123977661},{"id":"https://openalex.org/keywords/melanoma","display_name":"melanoma","score":0.9959999918937683},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.9309999942779541},{"id":"https://openalex.org/keywords/esophageal-cancer","display_name":"esophageal cancer","score":0.9900000095367432},{"id":"https://openalex.org/keywords/small-cell-lung-cancer","display_name":"small cell lung cancer","score":0.8989999890327454},{"id":"https://openalex.org/keywords/cell-cycle-dysregulation","display_name":"cell cycle dysregulation","score":0.7580000162124634},{"id":"https://openalex.org/keywords/tumor-growth-inhibition","display_name":"tumor growth inhibition","score":0.765999972820282},{"id":"https://openalex.org/keywords/mrna-translation","display_name":"mRNA translation","score":0.41499999165534973}],"concepts":[{"id":"https://openalex.org/C91965660","wikidata":"https://www.wikidata.org/wiki/Q415875","display_name":"Methyltransferase","level":4,"score":0.6330999732017517},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6327000260353088},{"id":"https://openalex.org/C207001950","wikidata":"https://www.wikidata.org/wiki/Q141124","display_name":"In vivo","level":2,"score":0.5961999893188477},{"id":"https://openalex.org/C149364088","wikidata":"https://www.wikidata.org/wiki/Q185917","display_name":"Translation (biology)","level":4,"score":0.5465999841690063},{"id":"https://openalex.org/C62112901","wikidata":"https://www.wikidata.org/wiki/Q189159","display_name":"Cell growth","level":2,"score":0.5230000019073486},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.5108000040054321},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.4878000020980835},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.48339998722076416},{"id":"https://openalex.org/C3675279","wikidata":"https://www.wikidata.org/wiki/Q211935","display_name":"Protein biosynthesis","level":2,"score":0.4648999869823456},{"id":"https://openalex.org/C33288867","wikidata":"https://www.wikidata.org/wiki/Q518328","display_name":"Methylation","level":3,"score":0.44279998540878296},{"id":"https://openalex.org/C29537977","wikidata":"https://www.wikidata.org/wiki/Q188941","display_name":"Cell cycle","level":3,"score":0.4271000027656555},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.38690000772476196},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.382999986410141},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.364300012588501},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.34769999980926514},{"id":"https://openalex.org/C153957851","wikidata":"https://www.wikidata.org/wiki/Q201448","display_name":"Transfer RNA","level":4,"score":0.3427000045776367},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.3310999870300293},{"id":"https://openalex.org/C81885089","wikidata":"https://www.wikidata.org/wiki/Q189082","display_name":"Cell culture","level":2,"score":0.3280999958515167},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.3231000006198883},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.31709998846054077},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.303600013256073},{"id":"https://openalex.org/C2777389519","wikidata":"https://www.wikidata.org/wiki/Q425088","display_name":"Temozolomide","level":3,"score":0.30149999260902405},{"id":"https://openalex.org/C2781230642","wikidata":"https://www.wikidata.org/wiki/Q492646","display_name":"Targeted therapy","level":3,"score":0.2870999872684479},{"id":"https://openalex.org/C195580219","wikidata":"https://www.wikidata.org/wiki/Q7251511","display_name":"Protein turnover","level":3,"score":0.28519999980926514},{"id":"https://openalex.org/C2776694085","wikidata":"https://www.wikidata.org/wiki/Q974135","display_name":"Chemotherapy","level":2,"score":0.2849000096321106},{"id":"https://openalex.org/C2780258809","wikidata":"https://www.wikidata.org/wiki/Q414143","display_name":"Gemcitabine","level":3,"score":0.2700999975204468},{"id":"https://openalex.org/C41091548","wikidata":"https://www.wikidata.org/wiki/Q26939","display_name":"Epigenetics","level":3,"score":0.2648000121116638},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.2578999996185303},{"id":"https://openalex.org/C119056186","wikidata":"https://www.wikidata.org/wiki/Q1431332","display_name":"Gene silencing","level":3,"score":0.2538999915122986}],"mesh":[],"locations_count":2,"locations":[{"id":"pmh:oai:www.repository.cam.ac.uk:1810/408445","doi":null,"is_oa":true,"landing_page_url":"https://www.repository.cam.ac.uk/handle/1810/408445","pdf_url":null,"source":{"id":"https://openalex.org/S4306401777","display_name":"Apollo (University of Cambridge)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I241749","host_organization_name":"University of Cambridge","host_organization_lineage":["https://openalex.org/I241749"],"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":null,"raw_type":"Article"},{"id":"doi:10.17863/cam.134595","doi":"https://doi.org/10.17863/cam.134595","is_oa":true,"landing_page_url":"https://doi.org/10.17863/cam.134595","pdf_url":null,"source":{"id":"https://openalex.org/S7407050737","display_name":"Apollo","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":"JournalArticle"}],"best_oa_location":{"id":"pmh:oai:www.repository.cam.ac.uk:1810/408445","doi":null,"is_oa":true,"landing_page_url":"https://www.repository.cam.ac.uk/handle/1810/408445","pdf_url":null,"source":{"id":"https://openalex.org/S4306401777","display_name":"Apollo (University of Cambridge)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I241749","host_organization_name":"University of Cambridge","host_organization_lineage":["https://openalex.org/I241749"],"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":null,"raw_type":"Article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[{"display_name":"Good health and well-being","score":0.8175585865974426,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1169555929","display_name":"A Discovery Research Tissue Scale Biology Platform (TSBP)","funder_award_id":"226795/Z/22/Z","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G2088980218","display_name":"Cambridge Stem Cell Institute","funder_award_id":"203151/A/16/Z","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G3717130484","display_name":null,"funder_award_id":"2022/FuF/001","funder_id":"https://openalex.org/F4320316047","funder_display_name":"Leukaemia UK"},{"id":"https://openalex.org/G5197108848","display_name":null,"funder_award_id":"2024/JGF/009","funder_id":"https://openalex.org/F4320316047","funder_display_name":"Leukaemia UK"},{"id":"https://openalex.org/G7403649556","display_name":"Cambridge Stem Cell Institute","funder_award_id":"203151/Z/16/Z","funder_id":"https://openalex.org/F4320311904","funder_display_name":"Wellcome Trust"},{"id":"https://openalex.org/G8458540392","display_name":null,"funder_award_id":"SEBCATP-2022/100009","funder_id":"https://openalex.org/F4320319985","funder_display_name":"Cancer Research UK"}],"funders":[{"id":"https://openalex.org/F4320311904","display_name":"Wellcome Trust","ror":"https://ror.org/029chgv08"},{"id":"https://openalex.org/F4320316047","display_name":"Leukaemia UK","ror":"https://ror.org/00xsz4758"},{"id":"https://openalex.org/F4320319985","display_name":"Cancer Research UK","ror":"https://ror.org/054225q67"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"The":[0,19],"N7-methylguanosine":[1],"(m7G)":[2],"modification":[3],"is":[4,166],"one":[5],"of":[6,32,40,57,68,71,114,127,135,151,163,170,178,188],"the":[7,15,30,37,53,125],"most":[8],"prevalent":[9],"tRNA":[10,65,164],"modifications,":[11],"mainly":[12],"catalysed":[13],"by":[14,105],"METTL1-WDR4":[16],"protein":[17],"complex1-4.":[18],"m7G":[20,110],"methyltransferase":[21,66],"METTL1":[22,136,179],"has":[23],"been":[24,48],"linked":[25],"to":[26],"oncogenic":[27,128],"transformation":[28],"and":[29,55,62,95,116,142,173],"maintenance":[31],"several":[33],"aggressive":[34,189],"malignancies;":[35],"however,":[36],"clinical":[38],"implications":[39],"therapeutically":[41],"targeting":[42,162],"a":[43,59,106,112,117,167,181,186],"tRNA-modifying":[44],"enzyme":[45],"have":[46],"not":[47],"established.":[49],"Here,":[50],"we":[51],"present":[52],"development":[54],"characterisation":[56],"STM9005,":[58],"highly":[60],"selective":[61,107],"potent":[63],"first-in-class":[64],"inhibitor":[67],"METTL1.":[69],"Treatment":[70],"numerous":[72],"cancer":[73,149],"cell":[74,85,90,97],"models":[75,150],"(including":[76],"leukaemia,":[77],"melanoma,":[78],"pancreatic":[79],"carcinoma,":[80],"oesophageal":[81],"cancer,":[82],"small":[83],"lung":[84],"carcinoma)":[86],"with":[87],"STM9005":[88],"blocks":[89],"growth,":[91],"causes":[92],"differentiation":[93],"changes":[94],"dysregulates":[96],"cycle":[98],"progression.":[99],"These":[100],"cellular":[101],"effects":[102],"were":[103],"accompanied":[104],"decrease":[108],"in":[109,119,137,146],"on":[111],"subset":[113],"tRNAs":[115],"reduction":[118],"their":[120],"expression":[121],"levels,":[122],"which":[123],"impacted":[124],"translation":[126],"mRNAs.":[129],"We":[130],"show":[131],"that":[132,161,175],"pharmacological":[133],"inhibition":[134,177],"vivo":[138],"impairs":[139],"tumour":[140],"growth":[141],"significantly":[143],"prolongs":[144],"survival":[145],"multiple":[147],"mouse":[148],"different":[152],"tissue":[153],"origin.":[154],"Collectively,":[155],"our":[156],"results":[157],"provide":[158],"strong":[159],"proof-of-concept":[160],"methylation":[165],"promising":[168],"avenue":[169],"anti-cancer":[171],"therapy":[172],"illustrate":[174],"catalytic":[176],"represents":[180],"novel":[182],"therapeutic":[183],"strategy":[184],"against":[185],"number":[187],"malignancies.":[190]},"counts_by_year":[],"updated_date":"2026-10-14T16:39:01.820549","created_date":"2026-09-24T00:00:00"}