TY - JOUR
T1 - Antisense strategies for oncogene inactivation
AU - Stein, C. A.
AU - Benimetskaya, Luba
AU - Mani, S.
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2005/12
Y1 - 2005/12
N2 - Antisense oligonucleotides have been evaluated as antineoplastic agents in a series of clinical trials, with mixed results. However, phase III trials incorporating G3139, a phosphorothioate oligomer targeted to the initiation codon region of the bcl-2 mRNA, have recently been completed in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL). This article discusses the mechanism of the antisense effect and its dependence on the cellular internalization of oligonucleotides and the activity of RNase H. It also describes the properties, specific and nonspecific, of phosphorothioate oligonucleotides, the predominant species in current clinical trials, and discusses pharmacokinetic data obtained from earlier phase I and II trials employing these molecules. While the application of antisense technology to the treatment of human cancer is conceptually straightforward, in practice there are many complicated, mechanistically based questions that must be considered.
AB - Antisense oligonucleotides have been evaluated as antineoplastic agents in a series of clinical trials, with mixed results. However, phase III trials incorporating G3139, a phosphorothioate oligomer targeted to the initiation codon region of the bcl-2 mRNA, have recently been completed in advanced melanoma, myeloma, and chronic lymphocytic leukemia (CLL). This article discusses the mechanism of the antisense effect and its dependence on the cellular internalization of oligonucleotides and the activity of RNase H. It also describes the properties, specific and nonspecific, of phosphorothioate oligonucleotides, the predominant species in current clinical trials, and discusses pharmacokinetic data obtained from earlier phase I and II trials employing these molecules. While the application of antisense technology to the treatment of human cancer is conceptually straightforward, in practice there are many complicated, mechanistically based questions that must be considered.
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U2 - 10.1053/j.seminoncol.2005.09.003
DO - 10.1053/j.seminoncol.2005.09.003
M3 - Article
C2 - 16338422
AN - SCOPUS:28844454167
SN - 0093-7754
VL - 32
SP - 563
EP - 572
JO - Seminars in oncology
JF - Seminars in oncology
IS - 6
ER -