Targeted Strategies in the Treatment of Primary Gastric Lymphomas: From Rituximab to Recent Insights into Potential New Drugs
Targeted Strategies in the Treatment of Primary Gastric Lymphomas: From Rituximab to Recent Insights into Potential New Drugs
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DOI：
10.2174/09298673113209990235
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发表时间：
2014-03-01
影响因子：
4.1
通讯作者：
Guarini, Attilio
中科院分区：
文献类型：
--
作者：
Merchionne, Francesca;Iacopino, Pasquale;Guarini, Attilio
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，两种组织学类型更为常见，即弥漫性大 B 细胞 (DLBC) NHL 和粘膜相关淋巴组织 (MALT) NHL，占腺癌之后胃肿瘤的大部分。多年来，这些 PG 淋巴瘤的治疗包括单独或联合手术、化疗和放疗。然而，在过去的二十年中，我们对其发病机制和生物学认识的进步改变了治疗策略，至少在疾病的早期阶段是这样。除了通过根除幽门螺杆菌（被认为是主要病原体）使肿瘤消退成为可能之外，这一认识还为评估靶向治疗的疗效提供了坚实的基础，即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。特别是，对单克隆抗CD20抗体利妥昔单抗、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进行了评估。尽管在 NHL 的这一亚型中具有显着的抗肿瘤活性且毒性可控，但关于最佳剂量、最佳给药方案及其与常规化疗的组合仍然存在许多问题。本综述重点关注 PG-MALT 和 DLBC 淋巴瘤的发病机制，并讨论新药对这些患者预后和生存影响的临床试验结果，同时考虑潜在的新治疗靶点。
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.