Falduto Angela, Cimino Francesco, Speciale Antonio, Musolino Caterina, Gangemi Sebastiano, Saija Antonella, Allegra Alessandro
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy.
Division of Hematology, Department of General Surgery and Oncology, University of Messina, Messina, Italy.
Blood Rev. 2017 Jul;31(4):235-249. doi: 10.1016/j.blre.2017.02.005. Epub 2017 Feb 27.
The treatment of diffuse large B cell lymphoma (DLBCL) is generally based on multidrug chemotherapy, for instance the therapy with rituximab together with cyclophosphamide, vincristine, doxorubicin, and prednisone (R-CHOP). A significant proportion of DLBCL patients benefit from rituximab-based chemoimmunotherapy. However, among patients with DLBCL toxic effects due to therapy treatment are still very frequent, as well as inter-individual differences in the outcomes of patients even having similar stage, histological grade and histopathological type of the tumor. The present paper reviews the actual status of pharmacogenomics studies concerning gene polymorphisms that may affect response and tolerability to R-CHOP therapeutic regimen used to treat DLBCL. There are clear evidences that polymorphisms of genes codifying for protein are involved in cytotoxicity induced by R-CHOP regimen. Moreover, polymorphisms in genes encoding TNF-superfamily cytokines and proteins involved in controlling cellular cycle and tumor growth may be related to variability in efficacy of R-CHOP therapy in DLBCL patients. This knowledge emphasizes the clinical meaning and importance of pharmacogenetics in oncology. The main merit of our study seems to have tried for the first time a comprehensive review of gene polymorphisms that are involved in the response to an entire therapeutic protocol, R-CHOP, in a specific disease, DLBCL, rather than examining polymorphisms referred to individual drugs among themselves not connected or used to treat different pathological conditions. Indeed, it seems clear that only the analysis of a constellation of polymorphisms can really be useful in clinical practice, while knowledge of a single polymorphism seems to give a limited contribution to our ability to use genetic analysis to the management of patients with malignant blood disorders.
弥漫性大B细胞淋巴瘤（DLBCL）的治疗通常基于多药化疗，例如利妥昔单抗联合环磷酰胺、长春新碱、多柔比星和泼尼松（R-CHOP）的治疗方案。相当一部分DLBCL患者受益于基于利妥昔单抗的化疗免疫疗法。然而，在DLBCL患者中，治疗引起的毒性作用仍然非常常见，而且即使肿瘤分期、组织学分级和组织病理学类型相似的患者，其个体间的治疗结果差异也很大。本文综述了药物基因组学研究的现状，这些研究涉及可能影响用于治疗DLBCL的R-CHOP治疗方案的反应和耐受性的基因多态性。有明确证据表明，编码蛋白质的基因多态性与R-CHOP方案诱导的细胞毒性有关。此外，编码TNF超家族细胞因子的基因多态性以及参与控制细胞周期和肿瘤生长的蛋白质多态性可能与DLBCL患者R-CHOP治疗疗效的变异性有关。这一知识强调了药物遗传学在肿瘤学中的临床意义和重要性。我们研究的主要优点似乎是首次全面综述了特定疾病DLBCL中涉及对整个治疗方案R-CHOP反应的基因多态性，而不是单独研究与未关联或用于治疗不同病理状况的个别药物相关的多态性。事实上，很明显只有对一组多态性进行分析在临床实践中才真正有用，而单一多态性的知识似乎对我们利用基因分析来管理恶性血液病患者的能力贡献有限。
