Epstein-Barr virus (EBV) and Kaposi sarcoma-associated herpesvirus (KSHV) are
      gammaherpesviruses that are associated with a variety of human cancers, including a subset of
      lymphomas, carcinomas, and sarcomas. In tumors the virus typically exists in a latent state.
      In latently infected cells, the vast majority of viral genes are not expressed and there is
      little to no production of infectious virions. The virus replicates in tandem with cell
      division using cellular machinery. This highly restricted pattern of gene expression allows
      the virus to evade immune recognition and clearance.

      Currently, the treatment approach to virally-associated malignancies is no different than the
      treatment approach to the same tumors where there is no viral association. Yet, the presence
      of virus within these tumors offers an opportunity to develop virus-specific, targeted
      therapies in these diseases. Such therapies might not only be more effective but also less
      toxic. EBV- and KSHV-associated cancers are more common in patients with HIV, congenital
      immunodeficiencies, or other immunosuppression, such as transplant recipients. These patients
      in particular would benefit from more targeted treatment approaches to their malignancies,
      potentially sparing the toxicities of cytotoxic chemotherapy in an already immunocompromised
      patient population.

      Activation of lytic gene expression in virally-infected tumors may enhance tumor-specific
      cell killing through multiple mechanisms. Importantly, the cytotoxic effects of antiviral
      nucleoside analogues, such as acyclovir and its cogeners, depend on the activity of viral
      kinases which are only expressed during lytic replication. Because EBV(+) or KSHV(+) tumors
      are characterized by latent viral infection, these antiviral drugs as a single agent are not
      active in these tumors. However, if lytic gene expression could be activated in
      virally-associated tumors, this could render EBV(+) and KSHV(+) tumor cells susceptible to
      killing by antiviral nucleoside analogues.

      Nelfinavir (NFV), an FDA-approved protease inhibitor for the treatment of HIV, has been shown
      to be a potent activator of lytic gene expression of EBV(+) and KSHV(+) cancer cell lines.
      Furthermore, NFV is able to activate lytic gene expression of EBV and KSHV at drug levels
      that are achievable in humans. There is also growing evidence that NFV has antitumor
      activity.

      The goals of this study is to determine if NFV activates lytic gene expression in the tumors
      and causes tumor regression in patients with EBV(+) or KSHV(+) cancers.