engleski

Circadian Rhythms and Personalized Melanoma Therapy

Disruption of the body circadian rhythms has been described in the pathogenesis of many health conditions including cancer. Aberrant circadian rhythms indeed, result in deregulation of circadian clock genes and proteins, which may alter cell proliferation and promote oncogenesis and cancer, including melanoma. Moreover, circadian rhythms are often involved in outcomes of anticancer therapy as well. At the molecular level, the mammalian circadian clock is controlled by transcriptional and posttranslational feedback loops comprising a set of key elements, so- called ‘clock genes’ involved in regulation of a wide range of circadian rhythms in physiological processes and behavior. So far, experimental evidence suggests alteration in circadian clock genes’ expression in human melanoma such as for example PER1, PER2, CLOCK and CRY1. However, no comprehensive data on the specific clock genes’ genetic alterations in melanoma were published so far. The current targeted melanoma therapy is mainly directed towards well-established general targets such as for example mutated BRAF and its signaling or towards immunological targets, namely cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Still, chronobiological intervention and its potential in melanoma treatment remain an unexploited area. In particular, optimization of melanoma therapy regimens according to the circadian rhythms or circadian clock function activation in melanoma by a particular therapy might represent a new therapeutic approach for treatment of malignant melanoma.

circadian rhythms ; clock genes ; melanoma ; personalized medicine ; chronotherapy

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