TY - JOUR
T1 - Time to stratify? the retinoblastoma protein in castrate-resistant prostate cancer
AU - Aparicio, Ana
AU - Den, Robert B.
AU - Knudsen, Karen E.
N1 - Funding Information:
The authors would like to thank Drs Chris Logothetis, Angelo DeMarzo, Adam Dicker, Leonard Gomella, Kevin Kelly, and Erik Knudsen, the Greater Philadelphia Prostate Cancer Working Group, and Matthew Schiewer for critical discussion and comments. We would also like to thank Ms Beth Schade for technical and artwork assistance. We regret omission of additional citations due to space constraints. The authors are supported by grants from the NIH (CA099996 and CA116777 to K. E. Knudsen), US Department of Defense (to R. B. Den), and the Prostate Cancer Foundation (to K. E. Knudsen and R. B. Den).
PY - 2011/10
Y1 - 2011/10
N2 - It is generally held that the retinoblastoma (RB) tumor suppressor functions in multiple tissues to protect against tumor development. However, preclinical studies and analysis of tumor samples of early disease did not support an important role of RB loss in the origin of prostate cancer. By contrast, recent observations in the clinical setting and subsequent modeling of RB function indicate that the tumor suppressor has specialized roles in controlling androgen receptor expression in prostate cancer, and primarily functions to prevent progression to the castration-resistant stage of disease. Furthermore, preclinical models have now shown that loss of RB expression or functional activity decreases the effectiveness of hormone therapy, yet seems to increase sensitivity to a subset of chemotherapeutic agents. Here, the current state of knowledge regarding the implications of RB loss for prostate cancer progression will be reviewed, and potential opportunities for developing RB as a metric to predict therapeutic response will be considered.
AB - It is generally held that the retinoblastoma (RB) tumor suppressor functions in multiple tissues to protect against tumor development. However, preclinical studies and analysis of tumor samples of early disease did not support an important role of RB loss in the origin of prostate cancer. By contrast, recent observations in the clinical setting and subsequent modeling of RB function indicate that the tumor suppressor has specialized roles in controlling androgen receptor expression in prostate cancer, and primarily functions to prevent progression to the castration-resistant stage of disease. Furthermore, preclinical models have now shown that loss of RB expression or functional activity decreases the effectiveness of hormone therapy, yet seems to increase sensitivity to a subset of chemotherapeutic agents. Here, the current state of knowledge regarding the implications of RB loss for prostate cancer progression will be reviewed, and potential opportunities for developing RB as a metric to predict therapeutic response will be considered.
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U2 - 10.1038/nrurol.2011.107
DO - 10.1038/nrurol.2011.107
M3 - Review article
C2 - 21811228
AN - SCOPUS:80054051518
SN - 1759-4812
VL - 8
SP - 562
EP - 568
JO - Nature Reviews Urology
JF - Nature Reviews Urology
IS - 10
ER -