Assinder Stephen J, Dong Qihan, Mangs Helena, Richardson Des R
Discipline of Physiology , School of Medical Sciences, Bosch Institute Prostate Cancer Focus Group, University of Sydney, Sydney, New South Wales, Australia.
Mol Pharmacol. 2009 Mar;75(3):429-36. doi: 10.1124/mol.108.053066. Epub 2008 Dec 3.
Prostate cancer is a highly heterogenous disease in which a patient-tailored care program is much desired. Central to this goal is the development of novel targeted pharmacological interventions. To develop these treatment strategies, an understanding of the integration of cellular pathways involved in both tumorigenesis and tumor suppression is crucial. Of further interest are the events elicited by drug treatments that exploit the underlying molecular pathology in cancer. This review briefly describes the evidence that suggests integration of three established pathways: the tumorigenic phosphoinositide 3-kinase/protein kinase B (AKT) pathway, the tumor suppressive phosphatase and tensin homolog deleted on chromosome 10 pathway, and the tumor suppressive transforming growth factor-beta pathway. More importantly, we discuss novel pharmaceutical agents that target key points of integration in these three pathways. These new therapeutic strategies include the use of agents that target iron to inhibit proliferation via multiple mechanisms and suppression of AKT by cytosolic phospholipase A(2)-alpha inhibitors.
前列腺癌是一种高度异质性疾病，非常需要针对患者量身定制的护理方案。实现这一目标的核心是开发新型靶向药物干预措施。要制定这些治疗策略，了解肿瘤发生和肿瘤抑制过程中涉及的细胞信号通路的整合情况至关重要。更值得关注的是药物治疗引发的事件，这些事件利用了癌症潜在的分子病理学特征。本综述简要描述了表明三种既定信号通路整合的证据：致癌性磷酸肌醇3激酶/蛋白激酶B（AKT）信号通路、肿瘤抑制性10号染色体缺失的磷酸酶和张力蛋白同源物信号通路，以及肿瘤抑制性转化生长因子-β信号通路。更重要的是，我们讨论了针对这三种信号通路整合关键点的新型药物。这些新的治疗策略包括使用通过多种机制靶向铁以抑制增殖的药物，以及使用胞质磷脂酶A2-α抑制剂抑制AKT。
