Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms?

IF 2.4 4区医学 Q2 ONCOLOGY

Current Opinion in Oncology Pub Date : 2025-07-01 Epub Date: 2025-05-16 DOI:10.1097/CCO.0000000000001158

Michel Meyers, Ioannis Karfis, Alain Hendlisz

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引用次数: 0

Abstract

Purpose of review: The purpose of this review is to evaluate the role of epigenetic-targeting approaches in the management of neuroendocrine neoplasms (NENs), particularly as a priming strategy for subsequent therapies. We explore the molecular basis of epigenetic modifications in NENs, and we review preclinical and clinical studies on DNA methyltransferase and histone deacetylase (HDAC) inhibitors.

Recent findings: DNA methyltransferase and HDAC inhibitors can upregulate SSTR2 expression, thereby improving radioligand uptake and treatment response in NENs. The LANTana study investigates ASTX727 as a strategy to restore SSTR2 expression in metastatic NENs, allowing previously ineligible patients to receive PRRT. Preclinical studies demonstrate that combining epigenetic agents with radiotherapy, chemotherapy, or targeted inhibitors can enhance tumour sensitivity and overcome resistance.

Summary: Epigenetic modifications play a crucial role in NENs, influencing tumour progression, therapy resistance, and SSTR2 expression. Epigenetic priming with DNA methyltransferase and HDAC inhibitors can enhance SSTR2 expression, improving the efficacy of PRRT in NENs. The LANTana study and other trials are investigating whether epigenetic-targeting approaches can be integrated into NEN treatment to optimize PRRT and overcome therapeutic limitations.

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表观遗传学靶向治疗神经内分泌肿瘤的时机准备好了吗？

综述目的：本综述的目的是评估表观遗传学靶向方法在神经内分泌肿瘤（NENs）治疗中的作用，特别是作为后续治疗的启动策略。我们探讨了NENs表观遗传修饰的分子基础，并综述了DNA甲基转移酶和组蛋白去乙酰化酶（HDAC）抑制剂的临床前和临床研究。最近的研究发现：DNA甲基转移酶和HDAC抑制剂可以上调SSTR2的表达，从而改善NENs的放射配体摄取和治疗反应。LANTana研究调查了ASTX727作为恢复转移性NENs中SSTR2表达的策略，允许先前不合格的患者接受PRRT。临床前研究表明，将表观遗传药物与放疗、化疗或靶向抑制剂联合使用可以增强肿瘤敏感性并克服耐药性。摘要：表观遗传修饰在NENs中起关键作用，影响肿瘤进展、治疗耐药性和SSTR2表达。表观遗传启动DNA甲基转移酶和HDAC抑制剂可以增强SSTR2的表达，提高PRRT在NENs中的疗效。LANTana研究和其他试验正在研究表观遗传靶向方法是否可以整合到NEN治疗中，以优化PRRT并克服治疗局限性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Opinion in Oncology 医学-肿瘤学

CiteScore

6.10

自引率

2.90%

发文量

130

审稿时长

4-8 weeks

期刊介绍： With its easy-to-digest reviews on important advances in world literature, Current Opinion in Oncology offers expert evaluation on a wide range of topics from sixteen key disciplines including sarcomas, cancer biology, melanoma and endocrine tumors. Published bimonthly, each issue covers in detail the most pertinent advances in these fields from the previous year. This is supplemented by annotated references detailing the merits of the most important papers.