Nikita Nikita, Sun Zhengyang, Sharma Swapnil, Shaver Amy, Seewaldt Victoria, Lu-Yao Grace
Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Cancers (Basel). 2025 Mar 3;17(5):866. doi: 10.3390/cancers17050866.
Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting chronic inflammation and shortening telomeres. These changes increase biological age, as seen in epigenetic clocks and biomarkers like p21, which also play roles in drug resistance and therapeutic decisions. Chronic inflammation, driven by higher levels of inflammatory cytokines such as TNF-α and IL-6 as well as telomere shortening, significantly contributes to the aging characteristics of breast cancer survivors. Non-coding RNAs, including microRNAs and long non-coding RNAs, are crucial in regulating gene expression and aging pathways altered by these treatments. This review explores new therapies targeting these epigenetic changes, like DNA methylation inhibitors, histone deacetylase inhibitors, and microRNA-based treatments, to reduce the aging effects of cancer therapy. Non-drug approaches, such as dietary changes and lifestyle modifications, also show promise in combating therapy-induced aging. It also highlights the clinical signs of aging-related side effects, such as heart and lung problems, endocrine and reproductive issues, and reduced quality of life. The development of comprehensive methods like the CHEMO-RADIAT score to predict major cardiovascular events after therapy is discussed. Understanding the epigenetic changes caused by breast cancer therapies offers valuable insights for creating interventions to enhance the health span and quality of life for survivors. Continued research is crucial to fully understand these epigenetic alterations and their long-term health impacts.
乳腺癌治疗显著提高了生存率，但其长期影响，尤其是对老年幸存者的影响，需要仔细考量。本综述深入探讨乳腺癌治疗与衰老如何相互交织，重点关注化疗、放疗、激素治疗和靶向治疗引发的表观遗传变化。这些治疗可通过改变DNA甲基化、组蛋白修饰和染色质重塑来加速生物衰老，在不改变DNA序列本身的情况下影响基因表达。该综述解释了治疗诱导的表观遗传修饰的双刃剑效应，即有助于对抗癌症但也加速衰老。特别是化疗和靶向治疗会影响DNA甲基化和组蛋白修饰，促进慢性炎症并缩短端粒。这些变化会增加生物年龄，如在表观遗传时钟和p21等生物标志物中所见，p21在耐药性和治疗决策中也发挥作用。由肿瘤坏死因子-α和白细胞介素-6等较高水平的炎性细胞因子驱动的慢性炎症以及端粒缩短，显著促成了乳腺癌幸存者的衰老特征。包括微小RNA和长链非编码RNA在内的非编码RNA在调节这些治疗改变的基因表达和衰老途径中至关重要。本综述探索了针对这些表观遗传变化的新疗法，如DNA甲基化抑制剂、组蛋白去乙酰化酶抑制剂和基于微小RNA的治疗，以减少癌症治疗的衰老效应。非药物方法，如饮食改变和生活方式调整，在对抗治疗诱导的衰老方面也显示出前景。它还强调了与衰老相关的副作用的临床症状，如心脏和肺部问题、内分泌和生殖问题以及生活质量下降。讨论了如CHEMO-RADIAT评分等综合方法的发展，以预测治疗后主要心血管事件。了解乳腺癌治疗引起的表观遗传变化为制定干预措施以延长幸存者的健康寿命和提高生活质量提供了宝贵的见解。持续研究对于充分理解这些表观遗传改变及其长期健康影响至关重要。
