TY - JOUR
T1 - Castration-resistant prostate cancer
T2 - Targeted therapies and individualized treatment
AU - Aggarwal, Rahul
AU - Ryan, Charles J.
PY - 2011/3
Y1 - 2011/3
N2 - Various molecular mechanisms have been implicated in the progression from hormone-sensitive to castration-resistant prostate cancer (CRPC). Novel targeted agents to treat CRPC have been developed that inhibit either androgen receptor (AR)-mediated signaling (AR antagonists and inhibitors of androgen synthesis) or non-AR-mediated signaling (inhibitors of Src, mammalian target of rapamycin, chaperone proteins, insulin-like growth factor-1 receptor, vascular endothelial growth factor, and endothelin-A receptor) pathways. However, variable efficacy has been observed in clinical trials, most likely because of the biologic heterogeneity of CRPC. To account for potential differences in disease biology, a more individualized approach to treatment, based on genomic and/or proteomic analyses of individual tumors, is being investigated. By identifying tumors with a characteristic molecular subtype and assigning treatment accordingly, it is hoped that a higher proportion of patients will benefit from targeted therapy. Additionally, lessons learned through the application of these technologies to prostate cancer may subsequently influence therapeutic development in other solid tumors.
AB - Various molecular mechanisms have been implicated in the progression from hormone-sensitive to castration-resistant prostate cancer (CRPC). Novel targeted agents to treat CRPC have been developed that inhibit either androgen receptor (AR)-mediated signaling (AR antagonists and inhibitors of androgen synthesis) or non-AR-mediated signaling (inhibitors of Src, mammalian target of rapamycin, chaperone proteins, insulin-like growth factor-1 receptor, vascular endothelial growth factor, and endothelin-A receptor) pathways. However, variable efficacy has been observed in clinical trials, most likely because of the biologic heterogeneity of CRPC. To account for potential differences in disease biology, a more individualized approach to treatment, based on genomic and/or proteomic analyses of individual tumors, is being investigated. By identifying tumors with a characteristic molecular subtype and assigning treatment accordingly, it is hoped that a higher proportion of patients will benefit from targeted therapy. Additionally, lessons learned through the application of these technologies to prostate cancer may subsequently influence therapeutic development in other solid tumors.
KW - Androgen receptor
KW - Investigational treatments
KW - Prostatic neoplasms
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=79953012441&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79953012441&partnerID=8YFLogxK
U2 - 10.1634/theoncologist.2010-0216
DO - 10.1634/theoncologist.2010-0216
M3 - Article
C2 - 21339259
AN - SCOPUS:79953012441
SN - 1083-7159
VL - 16
SP - 264
EP - 275
JO - Oncologist
JF - Oncologist
IS - 3
ER -