Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: a proof-of-concept, first-in-human dose study.

Journal article

PURPOSE: Enhanced tumor cell survival through expression of inhibitors of apoptosis (IAP) is a hallmark of cancer. Survivin, an IAP absent from most normal tissues, is overexpressed in many malignancies and associated with a poorer prognosis. We report the first-in-human dose study of LY2181308, a second-generation antisense oligonucleotide (ASO) directed against survivin mRNA. PATIENTS AND METHODS: A dose-escalation study evaluating the safety, pharmacokinetics, and pharmacodynamics of LY218...

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Authors: Talbot, D; Ranson, M; Davies, J; Lahn, M; Callies, S

• Publication status: Published
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research
• Volume: 16
• Issue: 24
• Pages: 6150-6158
• Publication date: 2010-12-01
• DOI: 10.1158/1078-0432.ccr-10-1932
• EISSN: 1557-3265
• ISSN: 1078-0432
• Language: English
• Keywords: Oligonucleotides; Pilot Projects; Inhibitor of Apoptosis Proteins; Male; Dose-Response Relationship, Drug; Aged; Female; Microtubule-Associated Proteins; Neoplasms; Aged, 80 and over; Gene Expression Regulation, Neoplastic; Genetic Therapy; Evidence-Based Practice; Middle Aged; Molecular Targeted Therapy; Antineoplastic Agents; Down-Regulation; Humans; Adult; Oligonucleotides, Antisense