Mechanisms navigating the TGF-β pathway in prostate cancer.
Mechanisms navigating the TGF-β pathway in prostate cancer.
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DOI：
10.1016/j.ajur.2015.04.011
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发表时间：
2015-01
影响因子：
2.6
通讯作者：
Kyprianou N
中科院分区：
文献类型：
--
作者：
Cao Z;Kyprianou N
目前几乎没有药物可用于治疗去势抵抗性前列腺癌（CRPC），对患者生存率的影响很低。转化生长因子-β（Transforming growth factor-β，TGF-β）是一种多功能多肽，在前列腺肿瘤的发生中具有相反的作用，在正常生长和早期疾病中是抑制剂，在晚期前列腺癌中是促进剂。TGF-β信号转导失调导致一系列有助于肿瘤发生的事件，包括增殖上调、凋亡减少、上皮向间质转化（EMT）和免疫监视逃避。TGF-β信号通路为建立CRPC治疗靶向平台提供了合适的场所。TGF-β效应子及其与雄激素轴通路的相互作用的研究将为目前抗雄激素治疗策略的耐药机制提供新的见解，并导致CRPC新的有效治疗模式的产生。TGF-β与关键致癌途径（包括丝裂原活化蛋白激酶（MAPK）和雄激素受体（AR））的功能会聚点被讨论为在肿瘤微环境中的EMT景观中导航。在此背景下，考虑了用于前列腺癌治疗的新兴抗TGF-β药物疗法。靶向TGF-β信号传导效应物与雄激素轴之间的功能性串扰支持开发用于以个性化医学方法治疗CRPC的高特异性和有效性的新型治疗策略。
Few pharmacotherapies are currently available to treat castration resistant prostate cancer (CRPC), with low impact on patient survival. Transforming growth factor-β (TGF-β) 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-β signaling leads to a cascade of events contributing to oncogenesis, including up-regulated proliferation, decreased apoptosis, epithelial-to-mesenchymal transition (EMT) and evasion of immune surveillance. TGF-β signaling pathway presents an appropriate venue for establishing a therapeutic targeting platform in CRPC. Exploitation of TGF-β 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-β 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-β pharmacotherapies for prostate cancer treatment are considered. Targeting the functional cross-talk between the TGF-β 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.