Department of Oncology, Haematology Unit, National Cancer Research Centre - Istituto Tumori Giovanni Paolo II, Viale Orazio Flacco, 65 70124 Bari, Italy.
Curr Med Chem. 2014;21(8):1005-16. doi: 10.2174/09298673113209990235.
Primary gastric non-Hodgkin's lymphomas (PG-NHL) are the most common extranodal lymphomas, representing between 47% and 74% of all gastrointestinal lymphoma cases. In Western countries two histological types, diffuse large B-cell (DLBC) NHL and mucosa-associated lymphoid tissue (MALT) NHL, are more frequently represented, accounting for the majority of gastric tumors after adenocarcinoma. For several years treatment of these PG lymphomas consisted of surgery, chemotherapy and radiotherapy, alone or in combination. In the last two decades however, advances in our understanding of their pathogenesis and biology have changed the treatment strategy, at least as regards the early stages of disease. In addition to making tumor regression possible through the eradication of Helicobacter pylori, which is considered the main pathogenic agent, this understanding has also provided a solid rationale to assess the efficacy of targeted therapy, namely of drugs which interfere with specific molecules expressed by tumor cells or are involved in key growth pathways of these lymphomas. In particular, rituximab, a monoclonal anti-CD20 antibody, radioimmunotherapy, the first-generation proteasome inhibitor bortezomib and lenalidomide have been evaluated. Despite significant antitumor activity in this subset of NHL and manageable toxicity, many questions still remain however about the optimal dose, the best administration schedule and their combination with conventional chemotherapy. This review focuses on the pathogenesis of PG-MALT and DLBC lymphomas, and discusses the results of clinical trials on the impact of new agents on prognosis and survival in these patients, considering also potential new therapautic targets.
原发性胃非霍奇金淋巴瘤（PG-NHL）是最常见的结外淋巴瘤，占所有胃肠道淋巴瘤病例的 47%至 74%。在西方国家，两种组织学类型，弥漫性大 B 细胞（DLBC）NHL 和黏膜相关淋巴组织（MALT）NHL，更为常见，占胃肿瘤的大多数，仅次于腺癌。多年来，这些 PG 淋巴瘤的治疗方法包括手术、化疗和放疗，单独或联合使用。然而，在过去的二十年中，我们对其发病机制和生物学的理解的进步改变了治疗策略，至少在疾病的早期阶段是这样。除了通过根除被认为是主要致病因子的幽门螺杆菌使肿瘤消退之外，这种理解还为评估靶向治疗的疗效提供了坚实的依据，即评估干扰肿瘤细胞表达的特定分子或参与这些淋巴瘤关键生长途径的药物的疗效。特别是，利妥昔单抗（一种抗 CD20 单克隆抗体）、放射免疫疗法、第一代蛋白酶体抑制剂硼替佐米和来那度胺已经得到了评估。尽管在这组 NHL 中具有显著的抗肿瘤活性和可管理的毒性，但关于最佳剂量、最佳给药方案以及与常规化疗联合使用的问题仍然存在。这篇综述重点讨论了 PG-MALT 和 DLBC 淋巴瘤的发病机制，并讨论了临床试验结果，这些结果涉及新药物对这些患者预后和生存的影响，同时也考虑了潜在的新治疗靶点。
