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Updated: Sep 13, 2025

VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
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Molecular Pathways and Targeted Therapies in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Jonathan Weiss1,2, Shannon A Carty1,2, Yasmin H Karimi1,2

  • 1Division of Hematology-Oncology, Department of Medicine, University of Michigan, Ann Arbor, MI 48109, USA.

Cancers
|July 29, 2025
PubMed

Insights

New therapies for relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) target key signaling pathways and extracellular proteins. This review discusses their successes and limitations in treating this aggressive B-cell malignancy.

Area of Science:

  • Oncology
  • Hematology
  • Immunology

Background:

  • Relapsed/refractory Diffuse Large B-cell Lymphoma (DLBCL) presents a significant therapeutic challenge.
  • Recent years have seen the approval of multiple novel agents for r/r DLBCL.
  • These agents target critical signaling pathways and cell surface proteins in malignant B-cells.

Purpose of the Study:

  • To review and discuss novel therapeutic agents for relapsed/refractory Diffuse Large B-cell Lymphoma.
  • To analyze therapies targeting key intracellular signaling pathways.
  • To highlight novel agents targeting extracellular proteins and their clinical impact.

Main Methods:

  • Literature review of approved and emerging therapies for r/r DLBCL.
  • Analysis of targeted pathways including B-cell receptor (BCR), Toll-Like Receptor (TLR), PI3K/AKT/mTOR, BCL-2, and XPO-1.
  • Examination of therapies targeting extracellular proteins such as CD19, CD20, CD30, ROR1, and PD-1.

Main Results:

  • Multiple novel agents targeting specific signaling pathways have demonstrated efficacy in r/r DLBCL.
  • Therapies directed at extracellular targets like CD19 and CD20 have shown significant clinical benefit.
  • Emerging agents targeting BCL-2 and XPO-1 represent promising avenues for treatment.

Conclusions:

  • A growing armamentarium of targeted therapies offers new hope for patients with r/r DLBCL.
  • Understanding the mechanisms of action and resistance is crucial for optimizing treatment strategies.
  • Continued research into novel pathways and combinations is essential to improve outcomes in DLBCL.
Keywords:
BCRCD19CD30PD-1ROR1TLRXPO-1immunotherapynon-Hodgkinssignalingtargeted therapy

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