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Ref Type Journal Article
PMID (26603261)
Authors Martínez-Vélez N, Xipell E, Vera B, Acanda de la Rocha A, Zalacain M, Marrodán L, Gonzalez-Huarriz M, Toledo G, Cascallo M, Alemany R, Patiño A, Alonso MM
Title The Oncolytic Adenovirus VCN-01 as Therapeutic Approach Against Pediatric Osteosarcoma.
Journal Clinical cancer research : an official journal of the American Association for Cancer Research
Vol 22
Issue 9
Date 2016 May 01
URL
Abstract Text Osteosarcoma is the most common malignant bone tumor in children and adolescents. Despite aggressive chemotherapy, more than 30% of patients do not respond and develop bone or lung metastasis. Oncolytic adenoviruses engineered to specifically destroy cancer cells are a feasible option for osteosarcoma treatment. VCN-01 is a replication-competent adenovirus specifically engineered to replicate in tumors with a defective RB pathway, presents an enhanced infectivity through a modified fiber and an improved distribution through the expression of a soluble hyaluronidase. The aim of this study is to elucidate whether the use of VCN-01 would be an effective therapeutic strategy for pediatric osteosarcoma.We used osteosarcoma cell lines established from patients with metastatic disease (531MII, 678R, 588M, and 595M) and a commercial cell line (143B). MTT assays were carried out to evaluate the cytotoxicity of VCN-01. Hexon assays were used to evaluate the replication of the virus. Western blot analysis was performed to assess the expression levels of viral proteins and autophagic markers. The antitumor effect of VCN-01 was evaluated in orthotopic and metastatic osteosarcoma murine animal models.This study found that VCN-01, a new generation genetically modified oncolytic adenovirus, administered locally or systemically, had a potent antisarcoma effect in vitro and in vivo in mouse models of intratibial and lung metastatic osteosarcoma. Moreover, VCN-01 administration showed a safe toxicity profile.These results uncover VCN-01 as a promising strategy for osteosarcoma, setting the bases to propel a phase I/II trial for kids with this disease. Clin Cancer Res; 22(9); 2217-25. ©2015 AACR.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
VCN-01 VCN-01 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
VCN-01 VCN-01 is a replication-competent oncolytic adenovirus that may lead to decreased tumor cell viability and reduced tumor growth (PMID: 26603261), particularly in tumors with a dysfunctional RB1 pathway (PMID: 30674657).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RB1 mutant osteosarcoma sensitive VCN-01 Preclinical - Cell line xenograft Actionable In a preclinical study, VCN-01 decreased viability of a human RB1-mutant primary osteosarcoma cell line in culture, and inhibited tumor growth and decreased lung metastases in xenograft models (PMID: 26603261). 26603261
Unknown unknown osteosarcoma not applicable VCN-01 Preclinical Actionable In a preclinical study, treatment with VCN-01 resulted in decreased viability of osteosarcoma cell lines in culture (PMID: 26603261). 26603261