New drug targets in Kaposi sarcoma

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.