The intricate relationship between cancer, circadian rhythms, and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression. Aging is a well-established primary risk factor for cancer, while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors. Moreover, aging itself disrupts circadian rhythms, leading to physiological changes that may accelerate cancer development. Despite these connections, the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature. In this review, we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development. We discuss how core circadian genes impact tumor risk and prognosis, highlighting the shared hallmarks of cancer and aging such as genomic instability, cellular senescence, and chronic inflammation. Furthermore, we examine the interplay between circadian rhythms and aging, focusing on how this crosstalk contributes to tumorigenesis, tumor proliferation, and apoptosis, as well as the impact on cellular metabolism and genomic stability. By elucidating the common pathways linking aging, circadian rhythms, and cancer, this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies. We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments, including chronotherapy and antiaging interventions, which may offer important benefits in the clinical management of cancer.

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

The expression of programmed cell death-ligand 1 (PD-L1) is being used as a predictive biomarker for immunotherapy in head and neck squamous cell carcinoma (HNSCC). Our study was a retrospective cohort that assessed PD-L1 expression levels through immunohistochemistry (IHC) in 119 surgical specimens from HNSCC patients. The expression of PD-L1 was evaluated by IHC staining using the monoclonal antibody 22C3 (Dako) and the combined positive score (CPS). The relationship between the PD-L1 expression and clinicopathologic features was analyzed. 107 cases (89.9%) and 52 cases (43.7%) were positive for PD-L1 expression when the CPS cutoff value was set at 1 and 20 respectively. The tumor stage (P = 0.022) and tumor site (P = 0.004) were significantly correlated with the PD-L1 expression (CPS ≥ 1). Non-diabetic patients (P = 0.046) were corelated to positive PD-L1 expression (CPS ≥ 20). When evaluating PD-L1 expression in 40 laryngeal squamous cell carcinomas (LSC), the nodal stage was found to be significantly associated with high expression of PD-L1 (CPS ≥ 20) (P = 0.042). As for 36 patients with hypopharyngeal squamous cell carcinomas (HPSC), the positive PD-L1 expression (CPS ≥ 1) were typically younger (P = 0.030) and patients without type II diabetes (P = 0.040). We evaluated all possible clinical prognostic factors in the univariate Cox model, and there was no significant correlation between clinical characteristics and survival. The results of our findings may help to understand the association between the PD-L1 expression and clinicopathological characteristics, and it showed no significant correlation between the expression of PD-L1 and OS in HNSCC.

The circadian clock is an internal timekeeper system that regulates biological processes through a central circadian clock and peripheral clocks controlling various genes. Basic helix–loop–helix ARNT-like 1 (BMAL1), also known as aryl hydrocarbon receptor nuclear translocator-like protein 1 (ARNTL1), is a key component of the circadian clock. The deletion of BMAL1 alone can abolish the circadian rhythms of the human body. BMAL1 plays a critical role in immune cell function. Dysregulation of BMAL1 is linked to immune-related diseases such as autoimmune diseases, infectious diseases, and cancer, and vice versa. This review highlights the significant role of BMAL1 in governing immune cells, including their development, differentiation, migration, homing, metabolism, and effector functions. This study also explores how dysregulation of BMAL1 can have far-reaching implications and potentially contribute to the onset of immune-related diseases such as autoimmune diseases, infectious diseases, cancer, sepsis, and trauma. Furthermore, this review discusses treatments for immune-related diseases that target BMAL1 disorders. Understanding the impact of BMAL1 on immune function can provide insights into the pathogenesis of immune-related diseases and help in the development of more effective treatment strategies. Targeting BMAL1 has been demonstrated to achieve good efficacy in immune-related diseases, indicating its promising potential as a targetable therapeutic target in these diseases.

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

The bladder and prostate originate from the urogenital sinus. However, bladder cancer (BC) is usually classified as an immune “hot” tumor, whereas prostate cancer (PCa) is deemed as an immune “cold” tumor according to the tumor microenvironment (TME) and clinical outcomes. To investigate the immune differences between BC and PCa, studies are compared focusing on immune regulation mediated by sex hormones and receptors to identify key genes and pathways responsible for the immune differences. From a developmental perspective, it is shown that PCa and BC activate genes and pathways similar to those in the developmental stage. During prostate development, the differential expression and function of the androgen receptor (AR) across cell types may contribute to its dual role in promoting and inhibiting immunity in different cells. Androgen deprivation therapy affects AR function in different cells within the TME, influencing immune cell infiltration and antitumor function. Additionally, estrogenα and estrogenβ exert contrasting effects in PCa and BC, which may hold the potential for modifying the “cold” and “hot” tumor phenotypes. Future research should target key genes and pathways involved in bladder development to clarify the immune regulatory similarities and differences between BC and PCa.