Yang Mei, Zhang Zhe, Nice Edouard C, Wang Chuang, Zhang Wei, Huang Canhua
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, PR China.
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Biochim Biophys Acta Rev Cancer. 2022 Jan;1877(1):188665. doi: 10.1016/j.bbcan.2021.188665. Epub 2021 Dec 9.
Psychological distress, such as chronic depression and anxiety, is a topical problem. In the context of cancer patients, prevalence rates of psychological distress are four-times higher than in the general population and often confer worse outcomes. In addition to evidence from epidemiological studies confirming the links between psychological distress and cancer progression, a growing body of cellular and molecular studies have also revealed the complex signaling networks which are modulated by psychological distress-derived chronic stress during cancer progression. In this review, aiming to uncover the intertwined networks of chronic stress-driven oncogenesis and progression, we summarize physiological stress response pathways, like the HPA, SNS, and MGB axes, that modulate the release of stress hormones with potential carcinogenic properties. Furthermore, we discuss in detail the mechanisms behind these chronic stimulations contributing to the initiation and progression of cancer through direct regulation of cancer hallmarks-related signaling or indirect promotion of cancer risk factors (including obesity, disordered circadian rhythms, and premature senescence), suggesting a novel research direction into cancer prevention and therapy on the basis of psychological interventions.
心理困扰,如慢性抑郁和焦虑,是一个热门问题。在癌症患者中,心理困扰的患病率比普通人群高四倍,且往往导致更差的预后。除了流行病学研究证实心理困扰与癌症进展之间的联系外,越来越多的细胞和分子研究也揭示了在癌症进展过程中由心理困扰衍生的慢性应激所调节的复杂信号网络。在本综述中,为了揭示慢性应激驱动肿瘤发生和进展的交织网络,我们总结了生理应激反应途径,如HPA、SNS和MGB轴,这些途径调节具有潜在致癌特性的应激激素的释放。此外,我们详细讨论了这些慢性刺激通过直接调节癌症特征相关信号或间接促进癌症风险因素(包括肥胖、昼夜节律紊乱和过早衰老)而导致癌症发生和进展的机制,这为基于心理干预的癌症预防和治疗提出了一个新的研究方向。