Posted on Apr 30, 2019, 8 p.m.
Interference with natural circadian rhythms has been found to promote tumour growth and to suppress effects of tumour fighting drugs, suggesting the need for chronotherapy which is the delivery of cancer drugs timed to the internal circadian rhythm.
Our internal circadian clock runs in the background of our brain, this keeps 24 hour time for changes in our physical and mental cycles in response to environmental cues such as dark and light; this natural rhythm regulates many important aspects of our lives.
Disruption of the circadian clock through sleep disturbances or shift work is a known risk factor for several forms of cancer for example, and hormonally induced circadian disruption is known to promote tumour growth in animal models, however the underlying mechanisms have not been clear.
Researchers from the University of Pennsylvania used the hormone dexamethasone to advance daily rhythms in cultured cells to investigate underlying mechanisms; treatment was found to alter expression of multiple genes, especially those involved with regulating cell cycle. In particular circadian rhythm disruption increased expression of cyclin D1 protein that activated cyclin D dependent kinase 4/6, which is a step that will ultimately lead to cell division.
Growth of a tumour is linked to cell division, as a result many treatments inhibit progression of cancer cell cycles. Tumour fighting PD-0332991 drug which inhibits CDK4/6 activity was found to vary according to the time of day; treatment was observed to be more effective during the morning than at night, and efficacy was reduced in mice with disrupted circadian rhythms as published in the journal PLOS Biology.
According to Amita Sehgal, “We suggest that chronic disruption of the normal circadian rhythm tips the balance between tumor-suppressive and tumor-progressive gene expression to favor tumor growth. Better understanding the molecular effects of jet lag, shift work, and other sources of chronic disruption may lead to strategies to minimize the increased cancer risk associated with these behaviors, and to better treatment strategies, including timing delivery of cancer therapy for maximum benefit.”