{"title":"放射治疗中的衰老和表观遗传学含义:BNCT的前景。","authors":"Chiara Papulino , Marco Crepaldi , Gregorio Favale , Nunzio Del Gaudio , Rosaria Benedetti , Angela Nebbioso , Michele Grieco , Marco Malavolta , Jacopo Sabbatinelli , Annalisa Capuano , Erika Martinelli , Giulia Martini , Valerio Nardone , Salvatore Cappabianca , Concetta Ambrosino , Giuseppe Paolisso , Lucia Altucci , Vincenzo Carafa","doi":"10.1016/j.arr.2025.102786","DOIUrl":null,"url":null,"abstract":"<div><div>Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT is a suitable strategy for elderly patients. However, despite its efficacy, variations in cell sensitivity to radiation influence treatment outcomes, and normal cells surrounding the tumor can also be affected. Radiation-induced DNA damage can trigger cellular senescence, a permanent cell cycle arrest with a pro-inflammatory secretory phenotype, contributing to tissue damage in healthy cells and radio-resistance in tumor cells. RT causes not only DNA breakage but also epigenetic remodeling. Epigenetic pathways are involved in RT response, and the radiosensitivity of tumor cells can be modulated using epigenetic compounds. Emerging treatments based on more precise forms of RT, such as boron neutron capture therapy (BNCT), offer promising results by selectively targeting tumors while potentially preserving healthy tissues. BNCT has shown efficacy in glioblastoma, recurrent head and neck carcinoma, and melanoma. This review i) examines the mechanisms and challenges of conventional RT, focusing on aging and its role in treatment efficacy and tolerability, ii) describes the impact of senescence and epigenetic factors on resistance, iii) explores advances in BNCT, and iv) considers the potential of epigenetic drugs to optimize RT outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102786"},"PeriodicalIF":12.4000,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"“Aging and epigenetic implications in radiotherapy: The promise of BNCT”\",\"authors\":\"Chiara Papulino , Marco Crepaldi , Gregorio Favale , Nunzio Del Gaudio , Rosaria Benedetti , Angela Nebbioso , Michele Grieco , Marco Malavolta , Jacopo Sabbatinelli , Annalisa Capuano , Erika Martinelli , Giulia Martini , Valerio Nardone , Salvatore Cappabianca , Concetta Ambrosino , Giuseppe Paolisso , Lucia Altucci , Vincenzo Carafa\",\"doi\":\"10.1016/j.arr.2025.102786\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT is a suitable strategy for elderly patients. However, despite its efficacy, variations in cell sensitivity to radiation influence treatment outcomes, and normal cells surrounding the tumor can also be affected. Radiation-induced DNA damage can trigger cellular senescence, a permanent cell cycle arrest with a pro-inflammatory secretory phenotype, contributing to tissue damage in healthy cells and radio-resistance in tumor cells. RT causes not only DNA breakage but also epigenetic remodeling. Epigenetic pathways are involved in RT response, and the radiosensitivity of tumor cells can be modulated using epigenetic compounds. Emerging treatments based on more precise forms of RT, such as boron neutron capture therapy (BNCT), offer promising results by selectively targeting tumors while potentially preserving healthy tissues. BNCT has shown efficacy in glioblastoma, recurrent head and neck carcinoma, and melanoma. This review i) examines the mechanisms and challenges of conventional RT, focusing on aging and its role in treatment efficacy and tolerability, ii) describes the impact of senescence and epigenetic factors on resistance, iii) explores advances in BNCT, and iv) considers the potential of epigenetic drugs to optimize RT outcomes.</div></div>\",\"PeriodicalId\":55545,\"journal\":{\"name\":\"Ageing Research Reviews\",\"volume\":\"110 \",\"pages\":\"Article 102786\"},\"PeriodicalIF\":12.4000,\"publicationDate\":\"2025-05-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Ageing Research Reviews\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1568163725001321\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ageing Research Reviews","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1568163725001321","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
“Aging and epigenetic implications in radiotherapy: The promise of BNCT”
Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT is a suitable strategy for elderly patients. However, despite its efficacy, variations in cell sensitivity to radiation influence treatment outcomes, and normal cells surrounding the tumor can also be affected. Radiation-induced DNA damage can trigger cellular senescence, a permanent cell cycle arrest with a pro-inflammatory secretory phenotype, contributing to tissue damage in healthy cells and radio-resistance in tumor cells. RT causes not only DNA breakage but also epigenetic remodeling. Epigenetic pathways are involved in RT response, and the radiosensitivity of tumor cells can be modulated using epigenetic compounds. Emerging treatments based on more precise forms of RT, such as boron neutron capture therapy (BNCT), offer promising results by selectively targeting tumors while potentially preserving healthy tissues. BNCT has shown efficacy in glioblastoma, recurrent head and neck carcinoma, and melanoma. This review i) examines the mechanisms and challenges of conventional RT, focusing on aging and its role in treatment efficacy and tolerability, ii) describes the impact of senescence and epigenetic factors on resistance, iii) explores advances in BNCT, and iv) considers the potential of epigenetic drugs to optimize RT outcomes.
期刊介绍:
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.