Does circadian rhythm influence gastrointestinal toxicity?

Abstract

Purpose of review The current review outlines the existing research on the impact of circadian rhythm on gastrointestinal toxicity associated with cancer treatment and explores clinical evidence for utilizing circadian-based approaches in addressing gastrointestinal symptoms such as nausea, vomiting, diarrhea, mucositis, and hepatotoxicity. Recent findings Recent evidence highlights circadian control of gastrointestinal physiology of appetite, digestion, nutrient absorption, and cellular proliferation in the digestive system. In addition, animal models support the mechanistic rationale of using chronotherapy (a type of anticancer therapy delivered at specific times with the goal of producing less toxicity and greater treatment response) to minimize gastrointestinal-impact of systemic cancer treatments. In addition, earlier research demonstrates that many chemotherapeutic agents are responsive to circadian timing in animals. On the contrary, clinical trials focused on minimizing gastrointestinal toxicity using chronotherapy have been limited in recent years and have not yielded the efficacy initially hoped for. Instead, researchers focused on understanding circadian rhythm's influence on the gastrointestinal system at a mechanistic level as well as measuring circadian rhythm at an individual level. Summary Although using circadian timing is a promising target for reducing gastrointestinal toxicity, recent evidence suggests that more research is needed to understand circadian rhythm before circadian-based interventions can be developed that will result in lessening of gastrointestinal toxicity.

A European pharmacogenomic study of the response to opioids in advanced cancer patients identifies germline variants associated with nausea-vomiting side effect

“…has not yet been reported, the in uence of circadian rhythm on gastrointestinal toxicity due to other cancer therapies (e.g., chemotherapy) is under investigation (as reviewed in 10 ). Nonetheless, it has been reported that NPAS2 might affect another common opioid side effect, i.e., the alteration of the sleep-wake cycle.…”

Holistic Needs Assessment of Cancer Survivors—Supporting the Process Through Digital Monitoring of Circadian Physiology

“…Elevated levels of circulating pro-inflammatory cytokines, induced by both cancer processes and anticancer treatments, which can alter the circadian coordination centrally, have been indeed shown to be associated with the clustering of fatigue and anorexia in cancer patients. 41 Circadian disruption could also account for digestive complaints, 101 sleep troubles, 102 and altered metabolism. 103 Thus, the accurate evaluation of circadian function through remote monitoring of cancer patients 83 could represent a biomarker of physiological and behavioral alteration, 75 a surrogate of symptom burden and of subjective complaints, 100 , 104 , 105 as well as a potential novel target of intervention, both pharmacological and behavioral.…”

Evaluation and Management of Sleep and Circadian Rhythm Disturbance in Cancer

“…Additionally, another broader therapeutic approach could involve the use of circadian-based anticancer treatments, which accounting for temporal oscillations in pharmacological and physiological determinants of drug effects aim at reducing toxicity and enhancing activity (101). However, despite the extensive experimental evidence showing a marked impact of time of administration of various class of anticancer drugs on their tolerance or efficacy (102), and trials supporting its clinical relevance as well (103,104), cancer chronotherapy is not yet routinely applied (105). Nonetheless, translational research avenues identifying determinants of personalised and precise chronotherapeutic schedules warrant dedicated novel trials to be developed with timing of drug administration as a fundamental aspect to optimize and improve patient outcomes (63).…”