The interplay between the PI3K/AKT pathway and circadian clock in physiologic and cancer-related pathologic conditions.

The circadian clock is responsible for the regulation of different cellular processes, and its disturbance has been linked to the development of different diseases, such as cancer. The main molecular mechanism for this issue has been linked to the crosstalk between core clock regulators and intracellular pathways responsible for cell survival. The PI3K/AKT signalling pathway is one of the most known intracellular pathways in the case of cancer initiation and progression. This pathway regulates different aspects of cell survival including proliferation, apoptosis, metabolism, and response to environmental stimuli. Accumulating evidence indicates that there is a link between the PI3K/AKT pathway activity and circadian rhythm in physiologic and cancer-related pathogenesis. Different classes of PI3Ks and AKT isoforms are involved in regulating circadian clock components in a transcriptional and functional manner. Reversely, core clock components induce a rhythmic fashion in PI3K and AKT activity in physiologic and pathogenic conditions. The aim of this review is to re-examine the interplay between this pathway and circadian clock components in normal condition and cancer pathogenesis, which provides a better understanding of how circadian rhythms may be involved in cancer progression.