Investigational New Drugs

, Volume 20, Issue 2, pp 145–158

Targeting Anti-Apoptotic Genes Upregulated by Androgen Withdrawal Using Antisense Oligonucleotides to Enhance Androgen- and Chemo-Sensitivity in Prostate Cancer

  • Martin E. Gleave
  • Toby Zellweger
  • Kim Chi
  • Hideaki Miyake
  • Satoshi Kiyama
  • Laura July
  • Simon Leung
Article

DOI: 10.1023/A:1015694802521

Cite this article as:
Gleave, M.E., Zellweger, T., Chi, K. et al. Invest New Drugs (2002) 20: 145. doi:10.1023/A:1015694802521

Abstract

The main obstacle to improved survival ofadvanced prostate cancer is our failure toprevent its progression to its lethal anduntreatable stage of androgen independence. New therapeutic strategies designed toprevent androgen-independent (AI)progression must be developed beforesignificant impact on survival can beachieved. Characterization of changes ingene expression profiles after androgenablation and during progression toandrogen-independence suggest that thevarious therapies used to kill neoplasticcells may precipitate changes in geneexpression that lead to the resistantphenotype. Castration-induced increases inantiapoptosis genes, Bcl-2 and clusterin,help create a resistant phenotype, whileantisense oligonucleotides can inhibitthese adaptive cell survival mechanisms andenhance both hormone and chemotherapy. Ongoing efforts are necessary to identify additionalmolecular pathways mediating AI progressionand chemoresistance, since complexities oftumor heterogeneity and adaptabilitydictate that optimal control over tumorprogression will require multi-targetsystemic therapies.

antisense oligonucleotide apoptosis Bcl-2 clusterin IGF-1 IGFBP prostate cancer taxol TRPM-2 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Martin E. Gleave
    • 1
  • Toby Zellweger
    • 1
  • Kim Chi
    • 1
  • Hideaki Miyake
    • 1
  • Satoshi Kiyama
    • 1
  • Laura July
    • 1
  • Simon Leung
    • 1
  1. 1.The Prostate Centre, Vancouver General Hospital, and Division of UrologyUniversity of British ColumbiaVancouverCanada

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