About this Research Topic
The daily fluctuations in metabolism, physiology and behavior of almost all living organisms are regulated by biological clocks. Biological rhythms with a period of about 24 hours are termed circadian rhythms. In mammals, control of the circadian rhythm is exercised by the main endogenous pacemaker, which is located in the suprachiasmatic nucleus (SCN) of the hypothalamus. This central clock synchronizes the rest of the body with internal and external cues through other clocks located in the brain and in peripheral tissues (the heart, skin or colon) that can generate fluctuations regardless of the SCN, although all are coordinated by it. Under physiologic conditions, presumably all mammalian cells in the body possess a functional circadian oscillator.
Many studies have linked circadian disruption and cancer development, including endocrine-dependent cancers. The tolerability and efficacy of radiotherapy and chemotherapy also depend on the circadian rhythms and the phase of the cell cycle in which they are administered. Mutations in molecular clock genes have been documented in many types of cancer. In addition, circadian rhythm may be altered or disrupted in many human cancers downstream of common oncogenic alterations, leading to altered oscillation of gene expression and metabolism. The complexity of the microenvironment and its cellular heterogeneity can also alters the expression of core circadian clock proteins in cancer cells.
Although the regulation of the expression of circadian rhythm genes appears to be mediated mainly by transcription-translation feed-back loops as well as by metabolic feed-back, the existence of other forms of non-transcriptional regulation has been demonstrated. Particularly, accumulating evidences have shown that miRNAs and SIRT1 are significant players in regulating various aspects of circadian clock function, such as epigenetics modifications of circadian genes. Fluctuations in cellular redox status, as a result of metabolic changes occurring in the tumor cell to adapt cellular bioenergetics to the cancer metabolic status, also modify the expression of circadian clock proteins. Interestingly, circadian rhythms control cell division and differentiation in normal stem cells. Cancer stem cells (CSCs) also generate rhythms that could be exploited with a chrono-pharmacological approach in which high-dosage treatments would be given at a circadian phase when these cells are most vulnerable.
In this Research Topic, we welcome original research contributions, short communications, review articles and commentaries aimed to discuss and improve our current knowledge on:
• The involvement, effects and relationship of circadian rhythms and microenvironment disruptions in each phase of tumorigenesis.
• Regulation of circadian rhythms in endocrine-related tumors.
• Pivotal role of circadian clock as a target for the development of new therapies for treatment of cancer.
Keywords: Endocrine cancer, circadian rhythms, microenvironment, chronotherapy, cancer stem cells
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.