Depression remodels tumor microenvironment to drive tumor progression: Bio-behavioural signalling pathways and clinical interventions
M. Y. Ge, Wenjin Zhang, Wenlong Zhang, Zixuan Zhang, Xiaobei Zeng, Deng Long, Meiyun Wen, Xiaorong Lu, Xian Shen, Zhiyong Li, Guangjiang Shi
Abstract
The conceptual framework of regulative effects depression on cancer biology. • Summarized a series of clinical, animal, cellular and molecular studies to provide a deeper understanding of the roles depression or chronic stress in regulating the tumor growth, angiogenesis, invasion and metastasis. • Discussed current understanding of depression changing the tumor microenvironment and addressed the newly identified biological mechanisms in tumor remodeling such as teamwork of immune cells, infiltration of nerve fibres and distribution of gut microbiota and summarize the potential targets in associated with these biological processes. • Identified clinical treatment challenges related to tumor with depression, and proposed some potential pharmacological interventions strategies that may be effectively to inhibit tumor progression, improve cancer outcomes and prolong survival. Depression, chronic stress, fear, and anxiety have been implicated as major risk factors in tumor growth, invasion, and metastasis. These psychological conditions stimulate the secretion of neurotransmitters and stress hormones through prolonged activation of the fight-or-flight response. The arousal of stress-related systems, such as the hypothalamic-pituitary-adrenocortical axis and the sympathetic nervous system, induces physiological alterations. Consequently, stress-associated mediators suppress antitumor immune responses, enhance the release of inflammatory cytokines, and promote tumor cell migration and survival within an altered tumor microenvironment through diverse signaling pathways. This review highlights recent advances in understanding how depression and chronic stress regulate tumor growth, angiogenesis, invasion, and metastasis. We further discuss how stress response systems remodel the tumor microenvironment to promote cancer progression, providing insights into the interface between behavioral and biological mechanisms and identifying potential therapeutic targets. We emphasize the rationale and importance of developing pharmacological interventions to inhibit tumor progression and enhance the efficacy of conventional therapies and immunotherapies in patients with cancer-associated depression. Moreover, we discuss emerging pharmacological strategies with the potential to prevent stress-related cancer progression.