期刊
ASIAN JOURNAL OF UROLOGY
卷 2, 期 1, 页码 11-18出版社
ELSEVIER SINGAPORE PTE LTD
DOI: 10.1016/j.ajur.2015.04.011
关键词
Transforming growth factor-beta; Prostate tumors; Androgen receptor; Epithelial-mesenchymal transition; Therapeutic value
资金
- NIH [RO1 DK 083761]
Few pharmacotherapies are currently available to treat castration resistant prostate cancer (CRPC), with low impact on patient survival. Transforming growth factor-beta (TGF-beta) is a multi-functional peptide with opposite roles in prostate tumorigenesis as an inhibitor in normal growth and early stage disease and a promoter in advanced prostate cancer. Dysregulated TGF-beta signaling leads to a cascade of events contributing to oncogenesis, including upregulated proliferation, decreased apoptosis, epithelial-to-mesenchymal transition (EMT) and evasion of immune surveillance. TGF-beta signaling pathway presents an appropriate venue for establishing a therapeutic targeting platform in CRPC. Exploitation of TGF-beta effectors and their cross talk with the androgen axis pathway will provide new insights into mechanisms of resistance of the current antiandrogen therapeutic strategies and lead to generation of new effective treatment modalities for CRPC. Points of functional convergence of TGF-beta with key oncogenic pathways, including mitogen-activated protein kinase (MAPK) and androgen receptor (AR), are discussed as navigated within the EMT landscape in the tumor microenvironment. In this context the emerging anti-TGF-beta pharmacotherapies for prostate cancer treatment are considered. Targeting the functional cross-talk between the TGF-beta signaling effectors with the androgen axis supports the development of novel therapeutic strategies for treating CRPC with high specificity and efficacy in a personalized-medicine approach. (C) 2015 Editorial Office of Asian Journal of Urology. Production and hosting by Elsevier (Singapore) Pte Ltd. This is an open access article under the CC BY-NC-ND license.
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