Targeting pathogenic mechanisms in marginal zone lymphoma: from concepts and beyond

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Marginal zone lymphoma (MZL) comprises three distinct lymphoid malignancies with an indolent course, often incurable except in early stages.
• Therapeutic progress for MZL is limited by small patient populations and reliance on treatments for other indolent lymphomas.

Purpose of the Study:

• To review potential therapeutic targets and pathways for directly inhibiting marginal zone lymphomagenesis.
• To discuss agents with theoretical applications in treating marginal zone lymphoma.

Main Methods:

• Review of current literature on molecular pathways implicated in MZL pathogenesis.
• Identification of targeted inhibitors and novel agents in development for MZL.

Main Results:

• Dysregulated pathways converge on nuclear factor κB (NF-κB) and the MYD88-IRAK4 axis, targeted by BTK and PI3K inhibitors.
• Novel agents targeting MALT1, SMAC, NIK, IRAK4, or MYD88 are under development.
• Epigenetic agents targeting hypermethylation, PRC2, TET2 mutations, EZH2, or HDACs are potential therapeutic tools.

Conclusions:

• Targeting NF-κB, B-cell receptor signaling, and NOTCH pathways offers promising therapeutic avenues for MZL.
• Epigenetic modifications in MZL suggest a role for epigenetic agents in treatment strategies.
• Further research and clinical trials are needed to validate these novel therapeutic approaches for marginal zone lymphoma.