Consideration of Sex as a Biological Variable in the Development of Doxorubicin Myotoxicity and the Efficacy of Exercise as a Therapeutic Intervention.
Consideration of Sex as a Biological Variable in the Development of Doxorubicin Myotoxicity and the Efficacy of Exercise as a Therapeutic Intervention.
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DOI：
10.3390/antiox10030343
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发表时间：
2021-02-25
期刊：
影响因子：
--
通讯作者：
Smuder AJ
中科院分区：
文献类型：
--
作者：
Montalvo RN;Doerr V;Nguyen BL;Kelley RC;Smuder AJ
阿霉素（DOX）是一种蒽环类抗生素，用于治疗多种血液学和实体肿瘤癌症。虽然DOX在减轻肿瘤负担方面非常有效，但由于对心脏和骨骼肌的不良反应，其临床应用受到限制。DOX对肌肉组织的有害影响与心力衰竭、呼吸困难、运动不耐受和生活质量降低的发生率增加有关，这在积极接受化疗的患者和癌症幸存者中都有报道。多种因素提高了dox相关患者发病的概率；然而，性别作为计算患者风险的生物学变量的作用仍不清楚。DOX肌毒性表现中性别二态性的不确定性源于解决这一问题的研究设计不充分。目前，大多数关于DOX肌毒性的临床数据来自男女比例不平衡的研究，其中一个性别被省略，和/或患者队列包括广泛的年龄范围。此外，对标准结果测量缺乏共识，对患者结果的长期评估困难，以及其他混杂因素（即癌症类型、药物组合、辅助治疗等），都排除了DOX肌毒性发生率在性别之间是否存在差异的明确答案。本文综述了目前有关DOX肌毒性发生率和严重程度的性别差异的临床和临床前文献，提出的DOX两性二态的机制，以及运动训练作为一种有效的治疗对策来保持男性和女性肌肉力量和功能的潜力。
Doxorubicin (DOX) is an anthracycline antibiotic used to treat a wide variety of hematological and solid tumor cancers. While DOX is highly effective at reducing tumor burden, its clinical use is limited by the development of adverse effects to both cardiac and skeletal muscle. The detrimental effects of DOX to muscle tissue are associated with the increased incidence of heart failure, dyspnea, exercise intolerance, and reduced quality of life, which have been reported in both patients actively receiving chemotherapy and cancer survivors. A variety of factors elevate the probability of DOX-related morbidity in patients; however, the role of sex as a biological variable to calculate patient risk remains unclear. Uncertainty regarding sexual dimorphism in the presentation of DOX myotoxicity stems from inadequate study design to address this issue. Currently, the majority of clinical data on DOX myotoxicity come from studies where the ratio of males to females is unbalanced, one sex is omitted, and/or the patient cohort include a broad age range. Furthermore, lack of consensus on standard outcome measures, difficulties in long-term evaluation of patient outcomes, and other confounding factors (i.e., cancer type, drug combinations, adjuvant therapies, etc.) preclude a definitive answer as to whether differences exist in the incidence of DOX myotoxicity between sexes. This review summarizes the current clinical and preclinical literature relevant to sex differences in the incidence and severity of DOX myotoxicity, the proposed mechanisms for DOX sexual dimorphism, and the potential for exercise training to serve as an effective therapeutic countermeasure to preserve muscle strength and function in males and females.
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影响因子：
6.1
作者：
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