The Achilles' heel of cancer survivors: fundamentals of accelerated cellular senescence.
The Achilles' heel of cancer survivors: fundamentals of accelerated cellular senescence.
复制标题
癌症幸存者的阿喀琉斯之踵：加速细胞衰老的基本原理。
DOI：
10.1172/jci158452
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发表时间：
2022-07-01
影响因子：
15.9
通讯作者：
Hashmi, Shahrukh K.
中科院分区：
文献类型：
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作者：
Shafqat, Shameel;Chicas, Evelyn Arana;Shafqat, Areez;Hashmi, Shahrukh K.
癌症治疗的最新进展延长了儿童和成人癌症幸存者的寿命。然而，癌症治疗会加速幸存者的衰老，这在临床上表现为慢性疾病的过早发病，例如内分泌疾病、骨质疏松症、心脏功能障碍、随后的癌症和老年衰弱综合征等。因此，癌症治疗引起的早期衰老导致癌症幸存者的发病率、死亡率和医疗支出显着增加。导致这种加速衰老的一个主要机制是细胞衰老。癌症治疗会诱导肿瘤细胞和正常非肿瘤组织的细胞衰老，从而有助于介导多种慢性疾病的发作。近年来，细胞衰老的临床监测和治疗靶向研究取得了长足的进展。目前大规模的临床试验正在评估衰老治疗药物，这些药物可以抑制或消除衰老细胞，以改善癌症治疗相关的衰老。在本文中，我们调查了有关癌症幸存者衰老表型和机制的最新文献，并对细胞衰老作为癌症幸存者加速衰老机制的主要临床前和转化证据进行了最新综述，并深入了解了衰老治疗药物的潜力。然而，只有随着时间的推移，细胞疗法对癌症幸存者的临床效果才会显现出来。
Recent improvements in cancer treatment have increased the lifespan of pediatric and adult cancer survivors. However, cancer treatments accelerate aging in survivors, which manifests clinically as the premature onset of chronic diseases, such as endocrinopathies, osteoporosis, cardiac dysfunction, subsequent cancers, and geriatric syndromes of frailty, among others. Therefore, cancer treatment–induced early aging accounts for significant morbidity, mortality, and health expenditures among cancer survivors. One major mechanism driving this accelerated aging is cellular senescence; cancer treatments induce cellular senescence in tumor cells and in normal, nontumor tissue, thereby helping mediate the onset of several chronic diseases. Studies on clinical monitoring and therapeutic targeting of cellular senescence have made considerable progress in recent years. Large-scale clinical trials are currently evaluating senotherapeutic drugs, which inhibit or eliminate senescent cells to ameliorate cancer treatment–related aging. In this article, we survey the recent literature on phenotypes and mechanisms of aging in cancer survivors and provide an up-to-date review of the major preclinical and translational evidence on cellular senescence as a mechanism of accelerated aging in cancer survivors, as well as insight into the potential of senotherapeutic drugs. However, only with time will the clinical effect of senotherapies on cancer survivors be visible.