{"doi":"10.4161/auto.22185","title":"The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4","abstract":null,"journal":"Autophagy","year":2012,"id":600079,"datarank":0.635115975689589,"base_score":4.23410650459726,"endowment":4.23410650459726,"self_citation_contribution":0.635115975689589,"citation_network_contribution":0.0,"self_endowment_contribution":0.635115975689589,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":68,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":299503,"name":"Sufi M. Thomas","orcid":"0000-0001-5370-0842","position":1,"is_corresponding":false},{"id":1538229,"name":"Elena T. Chan","orcid":null,"position":2,"is_corresponding":false},{"id":187706,"name":"Christopher J. Kirk","orcid":null,"position":3,"is_corresponding":false},{"id":1538231,"name":"Maria L. Freilino","orcid":null,"position":4,"is_corresponding":false},{"id":1538233,"name":"Hannah M. DeLancey","orcid":null,"position":5,"is_corresponding":false},{"id":94214,"name":"Jennifer R. Grandis","orcid":"0000-0002-1013-8965","position":6,"is_corresponding":false},{"id":1182324,"name":"Changyou Li","orcid":"0000-0002-0530-4228","position":7,"is_corresponding":false},{"id":103784,"name":"Daniel E. Johnson","orcid":"0000-0003-2505-530X","position":8,"is_corresponding":false},{"id":883674,"name":"Yan Zang","orcid":"0000-0002-6074-7179","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The next generation proteasome inhibitors carfilzomib and oprozomib activate prosurvival autophagy via induction of the unfolded protein response and ATF4","abstract":"The proteasome inhibitor bortezomib has shown remarkable clinical success in the treatment of multiple myeloma. However, the efficacy and mechanism of action of bortezomib in solid tumor malignancies is less well understood. In addition, the use of this first-in-class proteasome inhibitor is limited by several factors, including off-target effects that lead to adverse toxicities. We recently reported the impact and mechanisms of carfilzomib and oprozomib, second-in-class proteasome inhibitors with higher specificities and reduced toxicities, against head and neck squamous cell carcinoma (HNSCC). Carfilzomib and oprozomib potently inhibit HNSCC cell survival and the growth of HNSCC tumors. Both compounds promote upregulation of proapoptotic BIK and antiapoptotic MCL1, which serves to mediate and attenuate, respectively, the killing activities of these proteasome inhibitors. Both compounds also induce complete autophagic flux that is partially dependent on activation of the unfolded protein response (UPR) and upregulation of ATF4. Carfilzomib- and oprozomib-induced autophagy acts to promote HNSCC cell survival. Our study indicates that the therapeutic benefit of these promising proteasome inhibitors may be improved by inhibiting MCL1 expression or autophagy.","is_dataset_classified":null,"base_score":4.23410650459726,"endowment":4.23410650459726,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22995770","pmcid":"PMC3541310","openalex_id":"https://openalex.org/W1995092890","authors":[],"funders":[{"funder_name":"NCI NIH HHS","grant_id":"R01 CA137260","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P30 CA047904","title":null},{"funder_name":"NCI NIH HHS","grant_id":"P50 CA097190","title":null}],"total_grants":3,"fwci":3.1059,"citation_percentile":0.91251397,"influential_citations":0,"citation_trend":[{"year":2013,"count":3},{"year":2014,"count":11},{"year":2015,"count":2},{"year":2016,"count":12},{"year":2017,"count":9},{"year":2018,"count":2},{"year":2019,"count":8},{"year":2020,"count":2},{"year":2021,"count":5},{"year":2022,"count":3},{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://www.tandfonline.com/doi/pdf/10.4161/auto.22185?needAccess=true","host_type":"journal"},{"url":"https://www.tandfonline.com/doi/pdf/10.4161/auto.22185?needAccess=true","host_type":"publisher"},{"url":"http://www.tandfonline.com/doi/pdf/10.4161/auto.22185","host_type":"publisher"},{"url":"https://doi.org/10.4161/auto.22185","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22995770","host_type":"repository"},{"url":"https://escholarship.org/uc/item/23x1h988","host_type":"repository"},{"url":"http://europepmc.org/articles/PMC3541310","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3541310","host_type":"repository"}],"fields_of_study":["Autophagy in Disease and Therapy","Ubiquitin and proteasome pathways","Endoplasmic Reticulum Stress and Disease","Activating Transcription Factor 4","Autophagy","Boronic Acids","Bortezomib","Carcinoma, Squamous Cell","Cell Line, Tumor","Cell Survival","Head and Neck Neoplasms","Humans","Models, Biological","Oligopeptides","Proteasome Inhibitors","Pyrazines","Squamous Cell Carcinoma of Head and Neck","Unfolded Protein Response"],"mesh_terms":["Bortezomib","Squamous Cell Carcinoma of Head and Neck","Autophagy","Boronic Acids","Carcinoma, Squamous Cell","Cell Survival","Head and Neck Neoplasms","Humans","Models, Biological","Oligopeptides","Pyrazines","Cell Line, Tumor","Activating Transcription Factor 4","Unfolded Protein Response","Proteasome Inhibitors"],"keywords":["Carfilzomib","Bortezomib","Proteasome inhibitor","Autophagy","Proteasome","Downregulation and upregulation","MCL1","Cancer research","Biology","Unfolded protein response","Ixazomib","Programmed cell death","ATF4","Multiple myeloma","Pharmacology","Apoptosis","Cell biology","Immunology","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T12:10:46.843143Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}