{"doi":"10.1158/0008-5472.c.6500747","title":"Data from Ki-67 as a Molecular Target for Therapy in an <i>In vitro</i> Three-Dimensional Model for Ovarian Cancer","abstract":"<div>Abstract<p>Targeting molecular markers and pathways implicated in cancer cell growth is a promising avenue for developing effective therapies. Although the Ki-67 protein (pKi-67) is a key marker associated with aggressively proliferating cancer cells and poor prognosis, its full potential as a therapeutic target has never before been successfully shown. In this regard, its nuclear localization presents a major hurdle because of the need for intracellular and intranuclear delivery of targeting and therapeutic moieties. Using a liposomally encapsulated construct, we show for the first time the specific delivery of a Ki-67–directed antibody and subsequent light-triggered death in the human ovarian cancer cell line OVCAR-5. Photoimmunoconjugate-encapsulating liposomes (PICEL) were constructed from anti–pKi-67 antibodies conjugated to fluorescein 5(6)-isothiocyanate, as a photoactivatable agent, followed by encapsulation in noncationic liposomes. Nucleolar localization of the PICELs was confirmed by confocal imaging. Photodynamic activation with PICELs specifically killed pKi-67–positive cancer cells both in monolayer and in three-dimensional (3D) cultures of OVCAR-5 cells, with the antibody TuBB-9 targeting a physiologically active form of pKi-67 but not with MIB-1, directed to a different epitope. This is the first demonstration of (<i>a</i>) the exploitation of Ki-67 as a molecular target for therapy and (<i>b</i>) specific delivery of an antibody to the nucleolus in monolayer cancer cells and in an <i>in vitro</i> 3D model system. In view of the ubiquity of pKi-67 in proliferating cells in cancer and the specificity of targeting in 3D multicellular acini, these findings are promising and the approach merits further investigation. Cancer Res; 70(22); 9234–42. ©2010 AACR.</p></div>","journal":null,"year":2023,"id":404965,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8823,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1183316,"name":"Prakash Rai","orcid":"0000-0003-2337-6310","position":1,"is_corresponding":false},{"id":282750,"name":"Jonathan P. Celli","orcid":"0000-0003-3560-0770","position":2,"is_corresponding":false},{"id":282751,"name":"Imran Rizvi","orcid":"0000-0001-9673-4700","position":3,"is_corresponding":false},{"id":1183680,"name":"Bettina Baron‐Lühr","orcid":null,"position":4,"is_corresponding":false},{"id":1183681,"name":"Johannes Gerdes","orcid":null,"position":5,"is_corresponding":false},{"id":233099,"name":"Tayyaba Hasan","orcid":"0000-0003-0871-6057","position":6,"is_corresponding":false},{"id":539725,"name":"Ramtin Rahmanzadeh","orcid":"0000-0002-9329-8138","position":0,"is_corresponding":true}],"reference_count":36,"raw_metadata":null,"created_at":"2026-07-19T01:20:49.237119Z","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":[]}