title: Bortezomib-induced enzyme-targeted radiation therapy in herpesvirus-associated tumors.
abstract: We investigated the possibility of using a pharmacologic agent to modulate viral gene expression to target radiotherapy to tumor tissue. In a mouse xenograft model, we had previously shown targeting of [(125)I]2'-fluoro-2'-deoxy-beta-D-5-iodouracil-arabinofuranoside ([(125)I]FIAU) to tumors engineered to express the Epstein-Barr virus thymidine kinase (EBV-TK). Here we extend those results to targeting of a therapeutic radiopharmaceutical [(131)I]FIAU to slow or stop tumor growth or to achieve tumor regression. These outcomes were achieved in xenografts with tumors that constitutively expressed the EBV-TK. With naturally infected EBV tumor cell lines (Burkitt's lymphoma and gastric carcinoma), activation of viral gene expression by pretreatment with bortezomib was required. Marked changes in tumor growth could also be achieved in naturally infected Kaposi's sarcoma herpesvirus tumors after pretreatment with bortezomib. Bortezomib-induced enzyme-targeted radiation therapy illustrates the possibility of pharmacologically modulating tumor gene expression to result in targeted radiotherapy.
authors.affiliation: Department of Oncology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: De-Xue
authors.initials: DX
authors.lastname: Fu
authors.forename: Yvette
authors.initials: Y
authors.lastname: Tanhehco
authors.forename: Jianmeng
authors.initials: J
authors.lastname: Chen
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Foss
authors.forename: James J
authors.initials: JJ
authors.lastname: Fox
authors.forename: Ja-Mun
authors.initials: JM
authors.lastname: Chong
authors.forename: Robert F
authors.initials: RF
authors.lastname: Hobbs
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
authors.forename: George
authors.initials: G
authors.lastname: Sgouros
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Martin G
authors.initials: MG
authors.lastname: Pomper
authors.forename: Richard F
authors.initials: RF
authors.lastname: Ambinder
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001897:Boronic Acids / Q000494:pharmacology*; D000069286:Bortezomib; D002051:Burkitt Lymphoma / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D006566:Herpesviridae Infections / Q000532:radiotherapy; D004854:Herpesvirus 4, Human / Q000201:enzymology; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011719:Pyrazines / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000627:therapeutic use*; D012514:Sarcoma, Kaposi / Q000532:radiotherapy; D013274:Stomach Neoplasms / Q000532:radiotherapy*; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D007457:Iodine Radioisotopes; D011719:Pyrazines; D019275:Radiopharmaceuticals; D001086:Arabinofuranosyluracil; C043457:fialuridine; D000069286:Bortezomib; D013937:Thymidine Kinase
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