The Circadian Modulators as Molecular Targets in Cancer-A Review.

Disruptions in the circadian clock and their link with cancer constitute a growing area of research, as evidenced by the steadily increasing number of articles on the topic. While the genes associated with circadian rhythms are relatively well characterized, the complexity of their regulation remains an important direction for study. It has been demonstrated that the interplay between genes, their expression products and external factors, such as environmental pollutants and human behavioral patterns, can lead to pathological changes, including metabolic diseases and cancer. Investigation of circadian cycle deregulations can not only provide a better understanding of carcinogenicity mechanisms and risk assessment but also create possibilities to identify new chemotherapeutics targeted at neoplastic cells. REV-ERBs and RORs are two groups of circadian clock-related nuclear factors that are examined regarding their interactions with small-molecule modulators of the circadian clock. These can act as either receptor agonists or inverse agonists, depending on the specific characteristics of a particular cancer. This review therefore summarizes and systematizes existing knowledge regarding the effectiveness of circadian modulators as chemotherapy agents, with the aim of indicating further directions for research in the field.