放射治疗中的衰老和表观遗传学含义:BNCT的前景。

IF 12.4 1区 医学 Q1 CELL BIOLOGY
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
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引用次数: 0

摘要

尽管癌症治疗策略在近几十年来取得了相当大的进展,但选择性杀死肿瘤细胞同时尽量减少对健康组织的损害的挑战仍然存在。放疗(RT)仍然是肿瘤生长控制的关键,当联合手术,化疗和免疫治疗。RT的有效性取决于癌症类型、肿瘤特征以及外部或内部治疗的选择等因素。由于其无创性和低全身毒性,放疗是适合老年患者的策略。然而,尽管它有效,细胞对辐射敏感性的变化会影响治疗结果,肿瘤周围的正常细胞也会受到影响。辐射诱导的DNA损伤可引发细胞衰老,这是一种具有促炎分泌表型的永久性细胞周期停滞,有助于健康细胞的组织损伤和肿瘤细胞的放射抗性。RT不仅会导致DNA断裂,还会导致表观遗传重塑。表观遗传途径参与RT反应,肿瘤细胞的放射敏感性可以通过表观遗传化合物调节。基于更精确的放射治疗形式的新兴治疗方法,如硼中子捕获疗法(BNCT),通过选择性靶向肿瘤,同时潜在地保留健康组织,提供了有希望的结果。BNCT在胶质母细胞瘤、复发性头颈癌和黑色素瘤中显示出疗效。这篇综述i)探讨了传统RT的机制和挑战,重点是衰老及其在治疗疗效和耐受性中的作用,ii)描述了衰老和表观遗传因素对耐药性的影响,iii)探讨了BNCT的进展,iv)考虑了表观遗传药物优化RT结果的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
“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.
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
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.
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