title: Emerging therapeutic strategies for Epstein-Barr virus+ post-transplant lymphoproliferative disorder.
abstract: De novo malignancies represent an increasing concern in the transplant population, particularly as long-term graft and patient survival improves. EBV-associated B-cell lymphoma in the setting of PTLD is the leading malignancy in children following solid organ transplantation. Therapeutic strategies can be categorized as pharmacologic, biologic, and cell-based but the variable efficacy of these approaches and the complexity of PTLD suggest that new treatment options are warranted. Here, we review current therapeutic strategies for treatment of PTLD. We also describe the life cycle of EBV, addressing the viral mechanisms that contribute to the genesis and persistence of EBV+ B-cell lymphomas. Specifically, we focus on the oncogenic signaling pathways activated by the EBV LMP1 and LMP2a to understand the underlying mechanisms and mediators of lymphomagenesis with the goal of identifying novel, rational therapeutic targets for the treatment of EBV-associated malignancies.
authors.affiliation: Department of Surgery/Division of Abdominal Transplantation, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Olivia
authors.initials: O
authors.lastname: Hatton
authors.forename: Olivia M
authors.initials: OM
authors.lastname: Martinez
authors.forename: Carlos O
authors.initials: CO
authors.lastname: Esquivel
mesh_terms: D001402:B-Lymphocytes / Q000821:virology; D015967:Gene Expression Regulation, Viral; D006085:Graft Survival; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007167:Immunotherapy / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000628:therapy* / Q000821:virology*; D008954:Models, Biological; D016377:Organ Transplantation / Q000009:adverse effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011183:Postoperative Complications; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D000072377:Syk Kinase; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D014763:Viral Matrix Proteins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase