New drug targets in Kaposi sarcoma.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Beth Israel Deaconess Medical Center, Harvard Medical School, Division of Hematology/Oncology, Boston, MA 02215, USA. rsulliva@bidmc.harvard.edu
Ryan J
RJ
Sullivan
Liron
L
Pantanowitz
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use*; D018450:Disease Progression; D019288:Herpesvirus 8, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D015398:Signal Transduction
D000970:Antineoplastic Agents; D000998:Antiviral Agents