Chronotherapy is the science of modifying the timing of drugs to achieve the greatest benefit with the lowest risk of side effects. Importantly, a new study from the Weitzmann Institute finds the way our bodies function during the day could interfere with certain cancer medicines. The researchers discovered, for instance, that daytime hormone production interfered with epidermal growth factor receptors (EGFR), which are the proteins targeted by a class of anti-cancer drugs, such as the breast cancer treatment lapatinib. “These findings support a circadian clock-based paradigm in cancer therapy,” wrote the authors of the study.

Biological Time Clock

Our internal clock is actually a cluster of brain cells known as the suprachiasmatic nucleus, which is located in the hypothalmus. This internal clock times the different biological processes, including our body temperature and the cascade of different hormones. Because of the effects of these activities, our bodies do not respond to medications in the exact same way at different times throughout the day. While drugs may not become completely ineffectual if taken at the wrong moment, they may be less active in our systems or possibly less tolerated.

For the current study, the researchers conducted an animal experiment, treating different groups of mice with lapatinib at various times of day. Lapatinib and similar drugs work by blocking the activities of both EGFR and HER2, which are used by tumor cells to attract nutrients that help them survive. The mice treated with lapatinib at night showed significantly smaller tumors than those treated during the day. Because EGFR signalling is most strongly suppressed by hormones during the hours of the day, the scientists speculate that lower nighttime hormone production contributed to the drug's increased effectiveness.

Source: Lauriola M, Enuka Y, Zeisel A, et al. Diurnal suppression of ​EGFR signalling by glucocorticoids and implications for tumour progression and treatment. Nature Communications. 2014.