Abstract

Despite the great efforts for better treatment options for diffuse large B-cell lymphoma (DLBCL) (most common form of non-Hodgkin lymphoma, NHL) to treat and prevent relapse, it continues to be a challenge. Here, we present an overview of DLBCL and address the diagnostic assays and molecular techniques used in its diagnosis, role of biomarkers in detection, treatment of early and advanced stage DLBCL, and novel drug regimens. We discuss the significant biomarkers that have emerged as essential tools for stratifying patients according to risk factors and for providing insights into the use of more targeted and individualized therapeutics. We discuss techniques such as gene expression studies, including next-generation sequencing, which have enabled a more understanding of the complex pathogenesis of DLBCL and have helped determine molecular targets for novel therapeutic agents. We examine current treatment approaches, outline the findings of completed clinical trials, and provide updates for ongoing clinical trials. We highlight clinical trials relevant to the significant fraction of DLBCL patients who present with complex cases marked by high relapse rates. Supported by an increased understanding of targetable pathways in DLBCL, clinical trials involving specialized combination therapies are bringing us within reach the promise of an effective cure to DLBCL using precision medicine. Optimization of therapy remains a crucial objective, with the end goal being a balance between high survival rates through targeted and personalized treatment while reducing adverse effects in DLBCL patients of all subsets.

Highlights

  • Diffuse Large B-cell lymphoma (DLBCL), the most common subtype of lymphoma, accounts for up to 40% of non-Hodgkin adult lymphoma cases globally [1, 2]

  • The www.oncotarget.com down-regulation of miR-29 due to a translocation at t(3;7)(q27;q32) (Figure 1) involves the fusion of B-cell lymphoma 6 (BCL6) to a noncoding region of FRA7H, which suggests that miRNA replacement therapy might be effective for the treatment of diffuse large B-cell lymphoma (DLBCL) cases associated with loss of a specific miRNA [106, 108]

  • The results of this study indicate that disrupting B cell receptor (BCR)-induced signaling by inhibiting Spleen tyrosine kinase (Syk) represents a novel and successful therapeutic strategy for non-Hodgkin extranodal lymphoma (NHL) since patients’ median progression-free survival was 4.2 months [203]

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Summary

Introduction

Diffuse Large B-cell lymphoma (DLBCL), the most common subtype of lymphoma, accounts for up to 40% of non-Hodgkin adult lymphoma cases globally [1, 2]. The www.oncotarget.com down-regulation of miR-29 due to a translocation at t(3;7)(q27;q32) (Figure 1) involves the fusion of BCL6 to a noncoding region of FRA7H, which suggests that miRNA replacement therapy might be effective for the treatment of DLBCL cases associated with loss of a specific miRNA [106, 108].

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