Circadian Clock Modulation: A Novel Therapeutic Approach to Cancer Treatment and Management

There is a time code to the genome instructing temporal regulation of cellular activities. The time code is expressed in the form of circadian clocks composed of many transcription, co-activator, and co-repressor factors. The transcriptiontranslation feedback loops generated collectively by these factors regulate daily ~24- hour rhythms in physiology, metabolism, and behavior across divergent phyla. Genome-wide studies reflect that chronic disruption of circadian rhythms provides a plinth for the occurrence and progression of multiple diseases across our lifespan. Increasing epidemiological and experimental evidence are confirming that circadian clocks are compromised in cancer. Altered expression of circadian clock components is likely to be associated with the onset and progression of cancer. The concept of targeting circadian clocks at the molecular level is rapidly evolving and opening a new therapeutic window in cancer. Here we discuss the approaches and recent advancements that have been made for the identification and development of clockmodulating small molecules bearing drug-like properties for the therapeutics and therapeutic management of cancer. It is envisaged that this chapter will augment the concepts of precision medicine in general and circadian-related system anomalies.

Keywords: Cancer, Circadian clock, Clock-modulating small molecules, Drug like properties, Precision medicine, System anomalies, Time code.