Cancer Chronotherapeutics: Experimental, Theoretical, and Clinical Aspects

Apr 23, 2013Handbook of experimental pharmacology

Timing cancer treatments to the body's daily rhythms: lab studies, theories, and patient care

AI simplified

Circadian Biology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Circadian timing of drug administration may influence the tolerability of cancer chemotherapy by several folds.

The circadian timing system regulates various cellular processes, impacting how cancer treatments are tolerated.
Optimal delivery of anticancer drugs is often aligned with times of best tolerability, enhancing their effectiveness.
Mathematical models suggest that discrepancies in circadian and cell cycle dynamics between host and cancer cells explain variations in treatment response.
Clinical trials indicate significant improvements in tolerability with sinusoidal chronotherapy compared to other methods.
Factors such as sex, genetic background, and lifestyle can affect the ideal timing for chronotherapy.
Personalized circadian drug delivery seeks to enhance both tolerability and efficacy of treatments based on individual circadian rhythms.

AI simplified

The circadian timing system controls cell cycle, apoptosis, drug bioactivation, and transport and detoxification mechanisms in healthy tissues. As a consequence, the tolerability of cancer chemotherapy varies up to several folds as a function of circadian timing of drug administration in experimental models. Best antitumor efficacy of single-agent or combination chemotherapy usually corresponds to the delivery of anticancer drugs near their respective times of best tolerability. Mathematical models reveal that such coincidence between chronotolerance and chronoefficacy is best explained by differences in the circadian and cell cycle dynamics of host and cancer cells, especially with regard circadian entrainment and cell cycle variability. In the clinic, a large improvement in tolerability was shown in international randomized trials where cancer patients received the same sinusoidal chronotherapy schedule over 24h as compared to constant-rate infusion or wrongly timed chronotherapy. However, sex, genetic background, and lifestyle were found to influence optimal chronotherapy scheduling. These findings support systems biology approaches to cancer chronotherapeutics. They involve the systematic experimental mapping and modeling of chronopharmacology pathways in synchronized cell cultures and their adjustment to mouse models of both sexes and distinct genetic background, as recently shown for irinotecan. Model-based personalized circadian drug delivery aims at jointly improving tolerability and efficacy of anticancer drugs based on the circadian timing system of individual patients, using dedicated circadian biomarker and drug delivery technologies.

Full Text

Full text is available at the source.

View full text ↗

Cancer Chronotherapeutics: Experimental, Theoretical, and Clinical Aspects

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the circadian biology brief