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Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 28, 2023; 29(48): 6179-6197
Published online Dec 28, 2023. doi: 10.3748/wjg.v29.i48.6179
Gene targeted and immune therapies for nodal and gastrointestinal follicular lymphomas
Takuya Watanabe
Takuya Watanabe, Department of Internal Medicine and Gastroenterology, Watanabe Internal Medicine Aoyama Clinic, Niigata 9502002, Japan
Author contributions: Watanabe T solely contributed to this manuscript.
Conflict-of-interest statement: There is no conflict of interest to disclose.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Takuya Watanabe, MD, PhD, Director, Doctor, Department of Internal Medicine and Gastroenterology, Watanabe Internal Medicine Aoyama Clinic, 1-2-21 Aoyama, Nishi-ku, Niigata 9502002, Japan. nabetaku@dia-net.ne.jp
Received: September 24, 2023
Peer-review started: September 24, 2023
First decision: October 29, 2023
Revised: November 2, 2023
Accepted: December 18, 2023
Article in press: December 18, 2023
Published online: December 28, 2023
Processing time: 93 Days and 22.1 Hours
Abstract

Follicular lymphoma (FL) is the most common indolent B-cell lymphoma (BCL) globally. Recently, its incidence has increased in Europe, the United States, and Asia, with the number of gastrointestinal FL cases expected to increase. Genetic abnormalities related to t(14;18) translocation, BCL2 overexpression, NF-κB pathway-related factors, histone acetylases, and histone methyltransferases cause FL and enhance its proliferation. Meanwhile, microRNAs are commonly used in diagnosing FL and predicting patient prognosis. Many clinical trials on novel therapeutics targeting these genetic abnormalities and immunomodulatory mechanisms have been conducted, resulting in a marked improvement in therapeutic outcomes for FL. Although developing these innovative therapeutic agents targeting specific genetic mutations and immune pathways has provided hope for curative options, FL treatment has become more complex, requiring combinatorial therapeutic regimens. However, optimal treatment combinations have not yet been achieved, highlighting the importance of a complete under-standing regarding the pathogenesis of gastrointestinal FL. Accordingly, this article reviews key research on the molecular pathogenesis of nodal FL and novel therapies targeting the causative genetic mutations. Moreover, the results of clinical trials are summarized, with a particular focus on treating nodal and gastrointestinal FLs.

Keywords: Gastrointestinal follicular lymphoma; Genetic mutation analysis using next-generation sequencing; MicroRNA; Gene targeted therapy; Immune therapy

Core Tip: Recently, the incidence of follicular lymphoma (FL) has increased in Asia, Europe, and the United States, with the number of gastrointestinal FL cases expected to increase. This article reviews the recent literature on the molecular origins of, innovative treatments for, and clinical trial findings on FL, focusing on gastrointestinal FL. Genetic factors [e.g., t(14;18) translocation and B-cell lymphoma 2 overexpression] drive FL growth, while microRNAs aid in its diagnosis and prognosis. Although recent trials have reported enhanced treatment outcomes, curative therapies remain elusive, and combinatorial regimens have not been optimized. Hence, gastroenterologists require a more comprehensive understanding of gastrointestinal FL pathogenesis to facilitate improved therapeutic outcomes.