Abstract
The main obstacle to improved survival of advanced prostate cancer is our failure to prevent or treat its progression to its lethal and untreatable stage of androgen independence. New therapeutic agents designed to prevent androgen-independent progression are required. Accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents that specifically inhibit a progression-relevant target. Antisense oligonucleotides, short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene, promise to show enhanced specificity for malignant cells with a more favorable sideeffect profile due to well-defined and tailored modes of action. Although not all of the challenges have been met to date, emerging clinical evidence supports the premise that antisense oligonucleotides stand a realistic chance of emerging as major partners of rationally designed anti-cancer regimens. The status of antisense targeting of several genes, including bcl-2, bcl-xL, clusterin, androgen receptor and IGFBPs, relevant to prostate and other cancers, are reviewed.
Keywords: Hormone, Cytotoxic Therapies, androgen, anti-cancer regimens, oligonucleotides, clusterin, IGFBPs
Current Drug Targets
Title: Antisense Targets to Enhance Hormone and Cytotoxic Therapies in Advanced Prostate Cancer
Volume: 4 Issue: 3
Author(s): Martin Gleave, Colleen Nelson and Kim Chi
Affiliation:
Keywords: Hormone, Cytotoxic Therapies, androgen, anti-cancer regimens, oligonucleotides, clusterin, IGFBPs
Abstract: The main obstacle to improved survival of advanced prostate cancer is our failure to prevent or treat its progression to its lethal and untreatable stage of androgen independence. New therapeutic agents designed to prevent androgen-independent progression are required. Accelerated identification and characterization of cancer-relevant molecular targets has sparked considerable interest in the development of new generations of anti-cancer agents that specifically inhibit a progression-relevant target. Antisense oligonucleotides, short synthetic stretches of chemically modified DNA capable of specifically hybridizing to the mRNA of a chosen cancer-relevant target gene, promise to show enhanced specificity for malignant cells with a more favorable sideeffect profile due to well-defined and tailored modes of action. Although not all of the challenges have been met to date, emerging clinical evidence supports the premise that antisense oligonucleotides stand a realistic chance of emerging as major partners of rationally designed anti-cancer regimens. The status of antisense targeting of several genes, including bcl-2, bcl-xL, clusterin, androgen receptor and IGFBPs, relevant to prostate and other cancers, are reviewed.
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Cite this article as:
Gleave Martin, Nelson Colleen and Chi Kim, Antisense Targets to Enhance Hormone and Cytotoxic Therapies in Advanced Prostate Cancer, Current Drug Targets 2003; 4 (3) . https://dx.doi.org/10.2174/1389450033491190
DOI https://dx.doi.org/10.2174/1389450033491190 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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