Centre National de la Recherche UMR 5286, Centre de Recherche en Cancérologie de lyon, INSERM Unité Mixte de Recherche (UMR)-S1052 , Lyon, France.
DITEP, Gustave Roussy Cancer Campus , Villejuif, France.
Expert Opin Investig Drugs. 2020 Jun;29(6):555-566. doi: 10.1080/13543784.2020.1760245. Epub 2020 May 12.
Mantle cell lymphoma (MCL) is an aggressive B cell non-Hodgkin lymphoma (NHL) that is characterized by the translocation t(11;14)(q13;q32) and a poor response to rituximab-anthracycline-based chemotherapy. Intensive regimens offer durable response, but a subgroup of MCL patients will not be eligible for those regimens and hence are candidates for less toxic, novel therapies based on a more tailored personalized approach.
This article examines the molecular landscape of MCL, drug resistance mechanisms, and the data on emerging targeted therapies.
DNA damage pathway, ATM mutation, TP53, and epigenetic abnormalities are key drivers of MCL. sBCL2, PARP, ATR, CDK inhibitors or epigenetic modifiers are among the most promising drugs under investigation in clinical trials. The genomic landscape of MCL suggests two types of disease based on the presence of or alterations which should be the framework of future molecular driven strategies. Among novel drugs, those interacting with the DNA damage response pathway offer the most effective rational for their use in MCL.
套细胞淋巴瘤（MCL）是一种侵袭性 B 细胞非霍奇金淋巴瘤（NHL），其特征是易位 t（11；14）（q13；q32）以及对利妥昔单抗-蒽环类药物为基础的化疗反应不良。强化方案可提供持久的缓解，但一小部分 MCL 患者不符合这些方案的条件，因此是基于更具针对性的个性化方法的毒性较小、新型疗法的候选者。
本文研究了 MCL 的分子特征、耐药机制以及新兴靶向治疗的数据。
DNA 损伤途径、ATM 突变、TP53 和表观遗传异常是 MCL 的关键驱动因素。sBCL2、PARP、ATR、CDK 抑制剂或表观遗传修饰剂是临床试验中最有前途的药物之一。MCL 的基因组景观表明，根据存在或缺失改变，该病可分为两种类型，这应成为未来基于分子的治疗策略的框架。在新型药物中，那些与 DNA 损伤反应途径相互作用的药物为其在 MCL 中的应用提供了最有效的合理依据。
