title: The oncolytic adenovirus Δ24-RGD in combination with cisplatin exerts a potent anti-osteosarcoma activity.
abstract: Osteosarcoma is the most common malignant bone tumor in children and adolescents. The presence of metastases and the lack of response to conventional treatment are the major adverse prognostic factors. Therefore, there is an urgent need for new treatment strategies that overcome both of these problems. Our purpose was to elucidate whether the use of the oncolytic adenovirus Δ24-RGD alone or in combination with standard chemotherapy would be effective, in vitro and in vivo, against osteosarcoma. Our results showed that Δ24-RGD exerted a potent antitumor effect against osteosarcoma cell lines that was increased by the addition of cisplatin. Δ24-RGD osteosarcoma treatment resulted in autophagy in vitro that was further enhanced when combined with cisplatin. Of importance, administration of Δ24-RGD and/or cisplatin, in novel orthotopic and two lung metastatic models in vivo resulted in a significant reduction of tumor burden meanwhile maintaining a safe toxicity profile. Together, our data underscore the potential of Δ24-RGD to become a realistic therapeutic option for primary and metastatic pediatric osteosarcoma. Moreover, this study warrants a future clinical trial to evaluate the safety and efficacy of Δ24-RGD for this devastating disease.
authors.affiliation: Department of Medical Oncology, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain; Department of Pediatrics, Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain.
authors.forename: Naiara
authors.initials: N
authors.lastname: Martinez-Velez
authors.forename: Enric
authors.initials: E
authors.lastname: Xipell
authors.forename: Patricia
authors.initials: P
authors.lastname: Jauregui
authors.forename: Marta
authors.initials: M
authors.lastname: Zalacain
authors.forename: Lucía
authors.initials: L
authors.lastname: Marrodan
authors.forename: Carolina
authors.initials: C
authors.lastname: Zandueta
authors.forename: Beatriz
authors.initials: B
authors.lastname: Vera
authors.forename: Leire
authors.initials: L
authors.lastname: Urquiza
authors.forename: Luis
authors.initials: L
authors.lastname: Sierrasesúmaga
authors.forename: Mikel San
authors.initials: MS
authors.lastname: Julián
authors.forename: Gemma
authors.initials: G
authors.lastname: Toledo
authors.forename: Juan
authors.initials: J
authors.lastname: Fueyo
authors.forename: Candelaria
authors.initials: C
authors.lastname: Gomez-Manzano
authors.forename: Wensceslao
authors.initials: W
authors.lastname: Torre
authors.forename: Fernando
authors.initials: F
authors.lastname: Lecanda
authors.forename: Ana
authors.initials: A
authors.lastname: Patiño-García
authors.forename: Marta M
authors.initials: MM
authors.lastname: Alonso
mesh_terms: D000256:Adenoviridae / Q000502:physiology*; D000293:Adolescent; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002648:Child; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary; D008819:Mice, Nude; D009842:Oligopeptides / Q000627:therapeutic use*; D050504:Oncolytic Viruses / Q000502:physiology*; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy* / Q000648:ultrastructure; D023041:Xenograft Model Antitumor Assays
chemical_list: D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D002945:Cisplatin
keywords: AUTOPHAGY; ONCOLYTIC ADENOVIRUS; OSTEOSARCOMA