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Circadian rhythm-based cancer therapy in randomised clinical trials
1UniSA Allied Health & Human Performance, University of South Australia, Adelaide, Australia.
Introduction:
Since the 2017 Nobel Prize awarded to J. Hall, M. Rosbash and M.W. Young for their discoveries of molecular mechanisms behind the biological clock, circadian rhythm-based therapy, also known as chronotherapy, is receiving more attention in oncology and the number of anatomical sites of interest in this field is increasing. This observation is in line with the clinical evidence provided by trials on head and neck, lung, colorectal and cervical cancers, as well as the presently ongoing chronotherapy trials for breast and brain cancers.
Areas Covered:
The aim of this review was to collate all randomized trials conducted on chronotherapy for various tumor sites and to appraise the evidence for chrono-oncology to advance personalized therapy. Relevant literature was collected from Pubmed/Medline databases and from clinicatrials.gov.
Expert Opinion:
Current randomized clinical trials offer a certain level of evidence for the potential of chronotherapy to personalize oncologic treatment. However, comparison of trial results is hindered by the differences in timing of radiation/chemotherapy, the absence of harmonized recommendations for treatment outcome evaluation and not ultimately, the general lack of considering gender as a matched variable in trials, which was found to be a powerful factor influencing response to treatment.
Insights
Chronotherapy, or circadian rhythm-based therapy, shows promise in personalizing cancer treatment. However, variations in trial designs and lack of gender consideration hinder progress in this field.
Area of Science:
- Oncology
- Chronobiology
- Personalized Medicine
Background:
- The 2017 Nobel Prize highlighted molecular mechanisms of the biological clock.
- Circadian rhythm-based therapy (chronotherapy) is gaining traction in oncology.
- Clinical trials show promise across various cancer types, including head and neck, lung, colorectal, and cervical cancers.
Purpose of the Study:
- To review randomized clinical trials on chronotherapy for diverse tumor sites.
- To evaluate the evidence base for chrono-oncology in advancing personalized cancer therapy.
Main Methods:
- Literature search of Pubmed/Medline databases.
- Inclusion of data from clinicaltrials.gov.
- Systematic collation and appraisal of randomized trials.
Main Results:
- Current randomized trials provide evidence for chronotherapy's role in personalizing cancer treatment.
- Significant heterogeneity exists in trial methodologies, including treatment timing and outcome evaluation.
- Gender is a critical, yet often overlooked, variable influencing treatment response.
Conclusions:
- Chronotherapy holds potential for personalized oncologic treatment.
- Standardization of trial design and outcome measures is needed.
- Incorporating gender as a variable is crucial for optimizing chronotherapy efficacy.
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