Stress Hormones: Emerging Targets in Gynecological Cancers

Abstract

In the past decade, several discoveries have documented the existence of innervation in ovarian cancer and cervical cancer. Notably, various neurotransmitters released by the activation of the sympathetic nervous system can promote the proliferation and metastasis of tumor cells and regulate immune cells in the tumor microenvironment. Therefore, a better understanding of the mechanisms involving neurotransmitters in the occurrence and development of gynecological cancers will be beneficial for exploring the feasibility of using inexpensive β-blockers and dopamine agonists in the clinical treatment of gynecological cancers. Additionally, this article provides some new insights into targeting tumor innervation and neurotransmitters in the tumor microenvironment.

Association of Serum Concentrations of Testosterone and Insulin with the Degree of Cervical Squamous Intraepithelial Lesions in Cuban Women

“…Moreover, systemic use of glucocorticoids could increase the risk for HR-HPV persistence (OR, 2.04; 95% CI, 1.16-3.56) [65]. However, there are still contradictions between experimental and clinical studies on the involvement of glucocorticoids in the development of CxCa [66].…”

A systematic assessment of stress insomnia as the high-risk factor for cervical cancer and interplay of cervicovaginal microbiome

“…Physiological stresses like emotional perturbances, prolonged starvation, and physical trauma can highly disrupt homeostasis and may create a life-threatening condition. Cervical and ovarian cancer are the two major gynecological malignancies of women which are drastically influenced by physiological stressors ( Chen et al., 2021 ). A positive correlation between chronic stress and cervical cancer progression was drawn showed that long-term stress stimuli may activate the sympathetic nervous system and the HPA.…”

“…They are synthesized by immune and stromal cells, mainly endothelial cells and fibroblasts, and then they regulate cell growth, proliferation, differentiation, cell survival and death, immune cell activation, and cell migration ( Showalter et al., 2017 ). Chronic stressors critically impact on the cytokines profile as compared with chronic stress hormonal signaling ( Chen et al., 2021 ). In particular, the expression of IL-1, IL-2, IL-6, INF-γ, TNF-α, TGFβ, EGF, VEGF, and other growth factors are relatively more associated with chronic conditions as compared to other cytokines ( Ho et al., 2021 ; Lu et al., 2021 ; Zhou et al., 2021 ).…”

“…Whereas when pH increases it decreases the survival rate of the vaginal microbiome and reduces susceptibility towards viral infections ( Andralojc et al., 2021 ). The dynamic balance of the cervicovaginal microbiome could affect the host physiological, hormonal, and immune system via affecting the estrogen levels especially during menstruation and reproductive state ( Macintyre et al., 2015 ; Chen et al., 2021 ). Menopausal women lack of estrogen that causes an increase in anaerobic vaginal microflora and a decrease in Lactobacillus population, which affects the release of inflammatory cytokines, chemokines, and vaginal antimicrobial peptides ( Torcia, 2019 ).…”

Insights Into the Regulation of Gynecological Inflammation-Mediated Malignancy by Metalloproteinases

“…Gynecological malignancies, mainly comprised of cervical, ovarian, and endometrial cancers, contribute immensely to the worldwide cancer load, with cervical cancer being the fourth most common cancer in women ( Bray et al, 2018 ). The high mortality rate of gynecological cancers is majorly due to late diagnosis of the disease, chemoresistance, impaired apoptotic pathway, persistent inflammation, and aberrant MMP production ( Azevedo Martins et al, 2020 ; Carey et al, 2021 ; Chen et al, 2021 ). Inflammation is a process by which the innate immune system reacts to tissue injury or infection by bacteria, viruses, toxins, etc., and facilitates the recruitment of circulating cells by the adaptive immune system to the damaged tissue.…”