Investigating Correlates and Therapeutics of Fatigue in Cancer Patients

疲劳是一种多维症状，影响38%的社区个人和42%的初级保健患者。它是慢性病和癌症中最常见和最令人衰弱的症状之一。它对直接和间接的卫生经济成果产生了重大影响，估计每年损失的生产时间为3.3亿美元，主要是由于工作绩效降低。在癌症中，疲劳对日常活动，身体健康/功能以及与重要他人的关系产生了最大的负面影响。疲劳被描述为一种持续的，主观的疲劳感，干扰了正常的功能。它可以区别于正常的日常疲劳，因为它更频繁，无情，不可预测，并通过休息来解决。疲劳可能受到生理因素（例如，炎症或中枢神经系统功能障碍），心理社会因素（例如，抑郁或焦虑），和生活方式因素（例如，饮食、锻炼、饮酒、吸烟或社会角色）。疲劳还与其他症状共同发生（例如，疼痛、抑郁），导致症状负担，对患者的健康相关生活质量产生负面影响。疲劳的病因尚不清楚，但据信有中枢和外周成分。中枢性疲劳被假设是由于在运动过程中限制肌纤维募集的肾上腺素能途径引起的中枢神经系统驱动力降低，从而减少了肌肉糖酵解、氧消耗和心血管功能。外周疲劳是指即使神经驱动增加，特定肌肉也无法执行任务。这被认为是由动作电位故障、跨桥形成障碍或神经刺激增加中的兴奋收缩耦合故障引起的。尽管越来越多的文献表明这两种机制之间存在潜在的相互作用，但中枢和外周疲劳类型之间的相互作用仍不清楚。 研究小组继续招募参与者进行他们的研究，调查分子遗传相关性，以及癌症相关疲劳的可能治疗方法。该小组最近取得了与癌症治疗相关的多巴胺能受体激活相关的重大发现，这些受体触发炎症，这可能解释与癌症治疗相关的疲劳体验。正在通过临床研究、动物项目和体外实验进行进一步验证。PI正在与国家癌症研究所多学科前列腺癌诊所的合作者密切合作，继续招募研究受试者。该研究小组还与几个NIH核心实验室合作，以进一步开展研究。

Fatigue is a multidimensional symptom that impacts 38% of community-based individuals and 42% of primary care patients. It is one of the most common and most debilitating symptoms in chronic illness and in cancer. It has significant repercussions on both direct and indirect health economic outcomes, costing an estimated annual lost productive time of US$330 million mostly due to reduced work performance. In cancer, fatigue had the greatest negative impact on daily activity, physical well-being/function, and relationships with significant others. Fatigue is described as a persistent, subjective sense of tiredness that interferes with usual functioning. It can be distinguished from normal everyday tiredness, because it is more frequent, unrelenting, unpredictable, and unresolved by rest. Fatigue may be influenced by a combination of physiological factors (e.g., inflammation or central nervous system dysfunction), psychosocial factors (e.g., depression or anxiety), and lifestyle factors (e.g., diet, exercise, alcohol use, tobacco use, or social role). Fatigue also co-occurs with other symptoms (e.g., pain, depression) contributing to symptom burden, which negatively affects health-related quality of life of patients. The etiology of fatigue is unknown, but it is believed to have central and peripheral components. Central fatigue is hypothesized to result from a decrease in central nervous system drive brought about by serotonergic pathways limiting muscle fiber recruitment during exertion reducing muscle glycolysis, oxygen consumption, and cardiovascular function. Peripheral fatigue is the inability of a particular muscle to perform a task even with an increased neural drive. This is thought to be caused by an action potential failure, cross-bridge formation impairment, or excitation contraction coupling failure amidst increased neural stimulation. The interplay between central and peripheral types of fatigue remains unclear although an increasing body of literature has indicated a potential interaction of both mechanisms. The research team continues to enroll participants for their studies that investigate the molecular-genetic correlates, as well as possible therapeutics of cancer-related fatigue. The group recently made significant discoveries related to the activation of glutamatergic receptors associated with cancer therapy that trigger inflammation that may explain the fatigue experience related to cancer therapy. Further validation is being conducted through clinical studies, animal projects and in vitro experiments. The PI is working closely with collaborators from the Multidisciplinary Prostate Cancer Clinics of the National Cancer Institute to continue to recruit study participants. The study team is also collaborating with several NIH core laboratories to further their investigations.