TY - JOUR
T1 - Prostatic preneoplasia and beyond
AU - Joshua, A. M.
AU - Evans, A.
AU - Van der Kwast, T.
AU - Zielenska, M.
AU - Meeker, A. K.
AU - Chinnaiyan, A.
AU - Squire, J. A.
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
KW - Cancer genetics
KW - Carcinogenesis
KW - Disease progression
KW - Prostatic neoplasms
UR - http://www.scopus.com/inward/record.url?scp=42149122683&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=42149122683&partnerID=8YFLogxK
U2 - 10.1016/j.bbcan.2007.12.001
DO - 10.1016/j.bbcan.2007.12.001
M3 - Review article
C2 - 18166163
AN - SCOPUS:42149122683
SN - 0304-419X
VL - 1785
SP - 156
EP - 181
JO - Biochimica et Biophysica Acta - Reviews on Cancer
JF - Biochimica et Biophysica Acta - Reviews on Cancer
IS - 2
ER -