Infection with HHV8 has been linked to the occurrence of Kaposi’s sarcoma (KS) and several lymphoproliferative disorders, such as primary effusion lymphoma (PEL). The overall goal of this proposal is to test the efficacy of JQ1, a BRD4 inhibitor, alone and in combination with HSP90 inhibitor BIIB021, against KSHV associated primary effusion lymphomas using in vitro and in vivo studies. Collectively, the above studies will lay the groundwork for future clinical trials of JQ1 plus BIIB021 for the treatment of KSHV-associated malignancies.