Abstract
Antisense reagents and technology have developed as extraordinarily useful tools for analysis of gene function. The capacity of antisense to reduce expression of RNA (including protein-encoding mRNA and non-coding RNA) important in a multitude of diseases (including cancer) has led to the concept of using antisense molecules as drugs to treat those diseases. Both antisense RNA (RNAi) and antisense oligonucleotides (ASOs) are being developed for this purpose, with ASOs currently the most advanced in clinical testing. ASOs inhibit translation or induce degradation of complementary target RNA, and both Phase I and Phase II trials are either completed or in progress for a number of diseases. In this review, we focus on antisense approaches to treatment of two cancers (melanoma and hormone-resistant prostate cancer) where the early application of ASOs has provided important information revealing both potential for success and lessons for future preclinical and clinical investigation of ASOs as anti-cancer drugs. The progress of clinical application of two ASOs showing promise in treatment of human cancers –– Oblimersen(G3139), targeting BCL2 for the treatment of metastatic melanoma, and Custirsen (OGX-11), targeting clusterin for the treatment of hormone refractory prostate cancer (HRPC) – is examined.
Keywords: Antisense, BCL-2, G3139/ Oblimersen, melanoma, hormone-refractory prostate cancer (HRPC), Clusterin, OGX-11/custirsen
Current Cancer Drug Targets
Title: Antisense Treatment in Human Prostate Cancer and Melanoma
Volume: 10 Issue: 6
Author(s): C. Di Cresce and J. Koropatnick
Affiliation:
Keywords: Antisense, BCL-2, G3139/ Oblimersen, melanoma, hormone-refractory prostate cancer (HRPC), Clusterin, OGX-11/custirsen
Abstract: Antisense reagents and technology have developed as extraordinarily useful tools for analysis of gene function. The capacity of antisense to reduce expression of RNA (including protein-encoding mRNA and non-coding RNA) important in a multitude of diseases (including cancer) has led to the concept of using antisense molecules as drugs to treat those diseases. Both antisense RNA (RNAi) and antisense oligonucleotides (ASOs) are being developed for this purpose, with ASOs currently the most advanced in clinical testing. ASOs inhibit translation or induce degradation of complementary target RNA, and both Phase I and Phase II trials are either completed or in progress for a number of diseases. In this review, we focus on antisense approaches to treatment of two cancers (melanoma and hormone-resistant prostate cancer) where the early application of ASOs has provided important information revealing both potential for success and lessons for future preclinical and clinical investigation of ASOs as anti-cancer drugs. The progress of clinical application of two ASOs showing promise in treatment of human cancers –– Oblimersen(G3139), targeting BCL2 for the treatment of metastatic melanoma, and Custirsen (OGX-11), targeting clusterin for the treatment of hormone refractory prostate cancer (HRPC) – is examined.
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Cite this article as:
Di Cresce C. and Koropatnick J., Antisense Treatment in Human Prostate Cancer and Melanoma, Current Cancer Drug Targets 2010; 10 (6) . https://dx.doi.org/10.2174/156800910791859452
DOI https://dx.doi.org/10.2174/156800910791859452 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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