The Journal of biological chemistryAug 10, 2021

Links between the body's internal clock, cancer development, and timed chemotherapy

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

The circadian clock controls the expression of nearly 50% of protein coding genes in mice and likely in humans.

Disruption of the circadian clock is linked to serious health issues, including cancer.
Epidemiological studies show conflicting results regarding the link between circadian disruption from shift work and the incidence of various cancers.
Genetically engineered mice with clock disruption do not show higher rates of spontaneous or radiation-induced cancers compared to normal mice.
The molecular clock components are involved in regulating cellular functions such as the cell cycle and cell division.
Chronochemotherapy attempts have not shown improved outcomes despite expectations based on circadian biology.
Mapping DNA damage and repair in mice treated with cisplatin reveals potential insights for developing chronochemotherapy strategies.

Simplified

The circadian clock controls the expression of nearly 50% of protein coding genes in mice and most likely in humans as well. Therefore, disruption of the circadian clock is presumed to have serious pathological effects including cancer. However, epidemiological studies on individuals with circadian disruption because of night shift or rotating shift work have produced contradictory data not conducive to scientific consensus as to whether circadian disruption increases the incidence of breast, ovarian, prostate, or colorectal cancers. Similarly, genetically engineered mice with clock disruption do not exhibit spontaneous or radiation-induced cancers at higher incidence than wild-type controls. Because many cellular functions including the cell cycle and cell division are, at least in part, controlled by the molecular clock components (CLOCK, BMAL1, CRYs, PERs), it has also been expected that appropriate timing of chemotherapy may increase the efficacy of chemotherapeutic drugs and ameliorate their side effect. However, empirical attempts at chronochemotherapy have not produced beneficial outcomes. Using mice without and with human tumor xenografts, sites of DNA damage and repair following treatment with the anticancer drug cisplatin have been mapped genome-wide at single nucleotide resolution and as a function of circadian time. The data indicate that mechanism-based studies such as these may provide information necessary for devising rational chronochemotherapy regimens.

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Links between the body's internal clock, cancer development, and timed chemotherapy

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