{"title":"表观遗传学靶向治疗神经内分泌肿瘤的时机准备好了吗？","authors":"Michel Meyers, Ioannis Karfis, Alain Hendlisz","doi":"10.1097/CCO.0000000000001158","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>","PeriodicalId":10893,"journal":{"name":"Current Opinion in Oncology","volume":" ","pages":"377-382"},"PeriodicalIF":2.4000,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms?\",\"authors\":\"Michel Meyers, Ioannis Karfis, Alain Hendlisz\",\"doi\":\"10.1097/CCO.0000000000001158\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose of review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p><p><strong>Summary: </strong>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.</p>\",\"PeriodicalId\":10893,\"journal\":{\"name\":\"Current Opinion in Oncology\",\"volume\":\" \",\"pages\":\"377-382\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Opinion in Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/CCO.0000000000001158\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/5/16 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Opinion in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/CCO.0000000000001158","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/5/16 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Are epigenetic-targeting approaches ready for prime time in neuroendocrine neoplasms?
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.
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.
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