TY - JOUR
T1 - Signal transduction targets in androgen-independent prostate cancer
AU - Zhou, Jian
AU - Scholes, Jessica
AU - Hsieh, Jer Tsong
N1 - Funding Information:
This work is supported by a grant from the National Institute of Health (DK 4765707). We also thank Andrew Webb for editing the manuscript.
PY - 2001
Y1 - 2001
N2 - Prostate cancer (PCa) first manifests as an androgen-dependent disease. Thus, androgen-deprivation therapy is a standard regimen for patients with metastatic PCa. Despite the initial success of androgen-deprivation therapy, PCa inevitably progresses from being androgen dependent (AD) to androgen independent (AI), and this marks the poor prognosis of this disease. Relapse of AIPCa becomes life threatening and accounts for the majority of mortality of PCa patients. Currently, no effective therapy is available for controlling AIPCa. Therefore, the challenge in providing a new intervention is to understand the fundamental changes that occur in AIPCa. Increasing evidence indicates that, under androgen-deprived milieu, several signal networks elicited by peptide growth factors dictate the AI phenotype of PCa. This review covers the latest studies investigating the potential involvement of autocrine growth factors in cell proliferation, survival, metastasis, and the reciprocal interaction with the androgen receptor pathway. In addition, loss of the negative feedback mechanism of the signal cascade further amplifies the effect of growth factors, and thus contributes significantly to the onset of AIPCa. The understanding of the signal target(s) in AIPCa should provide the new markers for prognosis and a new strategy for prevention and therapy.
AB - Prostate cancer (PCa) first manifests as an androgen-dependent disease. Thus, androgen-deprivation therapy is a standard regimen for patients with metastatic PCa. Despite the initial success of androgen-deprivation therapy, PCa inevitably progresses from being androgen dependent (AD) to androgen independent (AI), and this marks the poor prognosis of this disease. Relapse of AIPCa becomes life threatening and accounts for the majority of mortality of PCa patients. Currently, no effective therapy is available for controlling AIPCa. Therefore, the challenge in providing a new intervention is to understand the fundamental changes that occur in AIPCa. Increasing evidence indicates that, under androgen-deprived milieu, several signal networks elicited by peptide growth factors dictate the AI phenotype of PCa. This review covers the latest studies investigating the potential involvement of autocrine growth factors in cell proliferation, survival, metastasis, and the reciprocal interaction with the androgen receptor pathway. In addition, loss of the negative feedback mechanism of the signal cascade further amplifies the effect of growth factors, and thus contributes significantly to the onset of AIPCa. The understanding of the signal target(s) in AIPCa should provide the new markers for prognosis and a new strategy for prevention and therapy.
KW - Androgen-independent prostate cancer
KW - Growth factor
KW - Prostate cancer
KW - Signal transduction
KW - Tumor suppressor
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U2 - 10.1023/A:1015504015302
DO - 10.1023/A:1015504015302
M3 - Review article
C2 - 12085971
AN - SCOPUS:0035740349
SN - 0167-7659
VL - 20
SP - 351
EP - 362
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 3-4
ER -