Prostatic preneoplasia and beyond

A. M. Joshua, A. Evans, T. Van der Kwast, M. Zielenska, A. K. Meeker, A. Chinnaiyan, J. A. Squire

Research output: Contribution to journalReview articlepeer-review

Abstract

Prostate cancer is a heterogeneous neoplasm both with regard to its development, molecular abnormalities and clinical course. For example, in the United States, 1 in 6 men is diagnosed with prostate cancer whilst only 1 in 34 dies of metastatic disease [A. Jemal, R. Siegel, E. Ward, T. Murray, J. Xu, M.J. Thun, Cancer Statistics, 2007, CA Cancer J. Clin. 57 (2007) 43-66]. In this review, we summarise novel understandings of the early molecular events in prostatic carcinogenesis that may underlie both the molecular and clinical heterogeneity. Issues covered include those related to stem cells and embryonic signalling, oncogene/tumor suppressor abnormalities, androgen signalling, apoptosis and the nature of tumor-stromal interactions. Emphasis is placed on signalling pathway abnormalities, their causation, consequences and interactions. For example, genomic abnormalities involving the TMPRSS2-ETS and PTEN loci and the resulting signalling effects suggest the importance of genomic instability as a crucial factor in the emergence of this neoplasm. Together with new insights into signalling pathways consequent to abnormalities such as these, a greater understanding of the pathophysiology involved in prostatic carcinogenesis will lead to targeted approaches for both therapy and chemoprevention in the future.

Original languageEnglish (US)
Pages (from-to)156-181
Number of pages26
JournalBiochimica et Biophysica Acta - Reviews on Cancer
Volume1785
Issue number2
DOIs
StatePublished - Apr 1 2008

Keywords

  • Cancer genetics
  • Carcinogenesis
  • Disease progression
  • Prostatic neoplasms

ASJC Scopus subject areas

  • Oncology
  • Genetics
  • Cancer Research

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