Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Hematology/Oncology, Boston, MA 02215, USA.
Expert Opin Ther Targets. 2010 Dec;14(12):1355-66. doi: 10.1517/14728222.2010.532336. Epub 2010 Nov 2.
Kaposi sarcoma (KS) occurs as a result of Kaposi sarcoma-associated herpesvirus (KSHV) infection, typically in the context of an immunodeficient state such as coinfection with HIV or transplantation. Systemic treatment of KS has traditionally involved one of several chemotherapeutic agents either in combination or as single agents, which typically provides reasonable response rates and short-term control. However, recurrence of KS is common and progression-free intervals are short. For these reasons, new therapies are being sought.
This review describes the contemporary pathobiology of KS targets, current limitations of standard treatment options, and examines the findings of completed and ongoing clinical trials of novel, molecularly targeted treatments for patients with KS.
The reader will be presented with key clinicopathological characteristics and the pathogenesis of KS. Standard therapy for KS is reviewed including local, regional and systemic treatments. Molecular targets related to LANA-mediated and vGPCR-mediated signaling, angiogenesis, apoptosis and KSHV replication are discussed in detail. The reader will be provided with a compilation of agents, their mechanism of action, and results on various molecularly target agents in KS.
With the elucidation of novel pathogenic mechanisms of KS including KSHV replication, restoration of immune competence and signal transduction pathways utilized by KSHV in the propagation of KS, rational therapeutic targets have been identified.
卡波氏肉瘤(KS)是由卡波氏肉瘤相关疱疹病毒(KSHV)感染引起的,通常发生在免疫缺陷状态下,如 HIV 合并感染或移植。KS 的系统治疗传统上涉及几种化疗药物中的一种或几种联合或单一药物,这些药物通常提供合理的反应率和短期控制。然而,KS 的复发很常见,无进展间隔很短。出于这些原因,正在寻求新的治疗方法。
本综述描述了 KS 目标的当代病理生物学、标准治疗方案的当前局限性,并检查了针对 KS 患者的新型、分子靶向治疗完成和正在进行的临床试验的结果。
读者将获得 KS 的关键临床病理特征和发病机制。对 KS 的标准治疗进行了综述,包括局部、区域和全身治疗。详细讨论了与 LANA 介导和 vGPCR 介导信号、血管生成、细胞凋亡和 KSHV 复制相关的分子靶点。将为读者提供各种分子靶向药物在 KS 中的作用机制和结果的药物汇编。
随着对 KS 的新发病机制的阐明,包括 KSHV 复制、免疫功能恢复和 KSHV 在 KS 传播中利用的信号转导途径,已经确定了合理的治疗靶点。