Targeting pituitary tumors.
Targeting pituitary tumors.
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针对垂体肿瘤。
DOI：
10.1159/000110608
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Heaney,AnthonyP
中科院分区：
文献类型：
--
作者：
Heaney,AnthonyP
背景：垂体瘤是一种常见的肿瘤，通常在多年的潜伏期内生长。很少致命，治疗仍然需要多次细胞减灭术和/或放射治疗及其伴随的副作用。作为一种调节途径的疾病过程，垂体瘤提供了许多潜在的治疗靶点，许多，如膜多巴胺2和生长抑素受体，已被成功开发多年。核受体，如雌激素受体，过氧化物酶体增殖物激活受体和视黄酸受体，在垂体瘤中大量表达，并且出现了各种越来越有效和特异性的配体。针对垂体肿瘤转化基因的亚细胞疗法在垂体肿瘤治疗中也可能有一定的效用，尽管使用基因疗法靶向核蛋白的障碍仍然存在。其他新药物如多沙唑嗪，一种α-肾上腺素受体阻滞剂，似乎抑制核因子κ B（NF κ B）介导的核信号传导，表皮生长因子受体也可能代表这些良性但有问题的肿瘤的新的和安全的药物治疗。结论：对垂体瘤发病机制的了解不断增加，已经确定了可能导致新疗法的新蛋白质和途径。在药物基因组学分析研究的指导下，针对其他肿瘤类型开发的新型靶向治疗的经验性探索可能会揭示许多这些新型靶向药物在垂体瘤治疗中的效用。
Background: Pituitary tumors are common and usually grow insidiously over many years. Rarely fatal, treatment still requires multiple cytoreductive surgeries and/or radiation therapy with its attendant side effects. As a disease process of regulatory pathways, pituitary tumors offer numerous potential therapeutic targets, and many, such as the membranal dopamine 2 and somatostatin receptors, have been successfully exploited for many years. Nuclear receptors, such as the estrogen receptor, peroxisome proliferator-activating receptor and retinoic acid receptor, are abundantly expressed in pituitary tumors, and a variety of increasingly potent and specific ligands are emerging. Subcellular therapies aimed at the pituitary tumor transforming gene may also have some utility in pituitary tumor management, though obstacles to targeting nuclear proteins using gene therapy still exist. Other novel agents such as doxazosin, an α-adrenoceptor blocker that appears to inhibit nuclear signaling mediated by nuclear factor kappa-B (NFĸB), and epidermal growth factor receptor may also represent new and safe medical therapies for these benign but problematic tumors. Conclusions: Increased understanding regarding the etiopathogenesis of pituitary tumors has identified new proteins and pathways that may lead to novel therapies. Empiric exploration of novel targeted therapies developed for other tumor types, guided by pharmacogenomic profiling studies, will likely reveal the utility of many of these novel targeted agents in the treatment of pituitary tumors.