https://orcid.org/0000-0002-2104-0779
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ABSTRACT
Introduction
There are many genetic mutations involved in B-cell lymphomagenesis. These mutations contribute to the prognosis of B-cell lymphomas and can be used for and targeted for intervention.
Areas covered
This review provides an overview of targeted gene therapies for B-cell lymphoma that were newly approved or are under clinical development. These include, TP53 mutations and related pathways, such as BTK inhibitors, MDM2/4 inhibitors, and XPO1 inhibitors; new drugs targeting EZH2 mutations through competitive inhibition, such as tazemetostat and GSK126; BCL-2-targeted therapeutics, including venetoclax and ABT-263; BTK, IRAK 1/4, HCK, and myddosome complex that targets the MYD88 mutation and the related pathways. In addition, we have also discussed gene mutations that have been reported as potential therapeutic targets, such as TNFAIP3, CARD11.
Expert opinion
The mechanisms underlying the role of several genetic mutations in lymphomagenesis have been reported, and several studies have designed and developed drugs targeting these mutations. Many of these drugs have been approved for clinical use, while several are still under clinical development. Recent studies have identified additional genetic mutations and gene targets for BCL-2 treatment; however, effective molecular interventions targeting these new targets are yet to be developed.
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Supplemental material
Supplemental data for this article can be accessed here.
Article highlights
Gene mutations play important roles in the development and progression of B-cell lymphoma. Some gene mutations and their pathways have been thoroughly researched. New intervention strategies and drugs are being developed, such as targeting the TP53 gene mutation, EZH2 gene mutation, BCL-2 gene, and MYD88 gene mutation.
Several studies are exploring potential therapeutic genes, such as the TNFRSF14 gene and the TNFRSF13 gene.
The FDA has approved many targeted drugs for clinical use; however, the development of drug resistance and adverse side effects need to be considered. Further exploration of gene mutations contributing to disease progression and the underlying molecular mechanisms could aid in the development of a ‘precision attack’ strategy with low or no side effects.
Precise treatment of B-cell hematological malignancies depends on accurate diagnosis. An accurate diagnosis can be achieved by understanding the molecular mechanisms that drive disease progression. This would also aid in the development of individualized, precise treatment.
Although many of the targeted drugs mentioned in this article have entered into clinical trials, some of them have objective effects only in animal experiments and in vitro experiments, and only a few drugs have been approved by the FDA. Therefore, consolidated effort is needed for the development of effective novel treatment strategies.
Acknowledgments
The authors thank Ruiwen Gao and Shun Yao for their helpful review of the manuscript.
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.