Targeting the turnover of oncoproteins as a new avenue for therapeutics development in castration-resistant prostate cancer

Shan Wang, Dede N. Ekoue, Ganesh V. Raj, Ralf Kittler

Research output: Contribution to journalShort survey

Abstract

The current therapeutic armamentarium for castration-resistant prostate cancer (CRPC) includes second-generation agents such as the Androgen Receptor (AR) inhibitor enzalutamide and the androgen synthesis inhibitor abiraterone acetate, immunotherapies like sipuleucel-T, chemotherapies including docetaxel and cabazitaxel and the radiopharmaceutical radium 223 dichloride. However, relapse of CRPC resistant to these therapeutic modalities occur rapidly. The mechanisms of resistance to these treatments are complex, including specific mutations or alternative splicing of oncogenic proteins. An alternative approach to treating CRPC may be to target the turnover of these molecular drivers of CRPC. In this review, the mechanisms by which protein stability of several oncoproteins such as AR, ERG, GR, CYP17A1 and MYC, will be discussed, as well as how these findings could be translated into novel therapeutic agents.

Original languageEnglish (US)
Pages (from-to)86-96
Number of pages11
JournalCancer Letters
Volume438
DOIs
StatePublished - Dec 1 2018

Keywords

  • Androgen receptor
  • ERG
  • Oncoprotein
  • Prostate cancer
  • Protein turnover
  • Ubiquitination

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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