Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor - Emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma
Akt/TSC/mTOR activation by the KSHV G protein-coupled receptor - Emerging insights into the molecular oncogenesis and treatment of Kaposi's sarcoma
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DOI：
10.4161/cc.6.4.3843
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发表时间：
2007-02-15
期刊：
影响因子：
4.3
通讯作者：
Montaner, Silvia
中科院分区：
文献类型：
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作者：
Montaner, Silvia
卡波西氏肉瘤（KS）是一种神秘的血管肿瘤，在部分发展中国家已达到流行病的比例，是艾滋病人群发病率和死亡率的主要原因。不幸的是，KS仍然难以治疗，特别是在其最先进的临床表现。最近确定的KS相关疱疹病毒（KSHV或HHV 8）作为其病毒病原体，促使人们重新关注这种疾病的分子发病机制。新出现的证据现在指出，一个单一的KSHV基因，vGPCR，作为必不可少的KS发展，提供了一个独特的机会，暴露新的目标，治疗这种肿瘤。在这方面，最近的工作已经确定Akt/TSC/mTOR信号级联作为vGPCR肉瘤发生的关键途径。事实上，在KS动物模型中，用雷帕霉素药理学抑制mTOR在预防vGPCR肿瘤发生方面显示出有希望的结果。这些观察结果进一步证实了一致的报告，证明雷帕霉素（西罗莫司）作为移植后KS患者的免疫抑制和抗肿瘤解决方案的疗效。总的来说，这些数据表明，抑制Akt/TSC/mTOR信号通路可能为目前缺乏治疗选择的患者提供一种新的基于分子的治疗方法。
Kaposi's sarcoma (KS) is an enigmatic vascular neoplasm that has reached epidemic proportions in parts of the developing world and is a leading cause of morbidity and mortality among the AIDS population. Unfortunately, KS is still difficult to manage therapeutically, especially in its most advanced clinical manifestations. The recent identification of the KS-associated herpesvirus (KSHV or HHV8) as its viral etiologic agent has prompted renewed interest in the molecular pathogenesis of this disease. Emerging evidence now points to a single KSHV gene, vGPCR, as essential for KS development, providing a unique opportunity to expose new targets for the treatment of this tumor. In this regard, recent work has identified the Akt/TSC/mTOR signaling cascade as a critical pathway in vGPCR sarcomagenesis. Indeed, pharmacological inhibition of mTOR with rapamycin has shown promising results in preventing vGPCR tumorigenesis in an animal model for KS. These observations are further validated by coincident reports demonstrating the efficacy of rapamycin (sirolimus) as an immunossuppresive and anti-tumoral solution for posttrans plant KS patients. Collectively, these data suggest that inhibition of the Akt/TSC/mTOR signaling pathway may provide a novel molecular-based approach for the treatment of patients who currently have a paucity of therapeutic options.