With our social change toward a 24-hour society, a substantial proportion (ca. 27%) of workers is engaged in shift-work schedules. However, epidemiological studies have indicated that such shift-work schedules increase the risk of obesity, cancers, diabetes, and cardiovascular diseases. Circadian clock-related disorders are now prevalent in our society. In mammals, circadian rhythms in physiological function are regulated by a molecular oscillator consisting of circadian clock genes. Disruption of cellular circadian rhythms is well-recognized to be associated with cancer development and tumorigenesis; however, the underlying mechanism is not fully understood.
　Solid tumors are composed of phenotypically and functionally heterogeneous cells. Among them, highly tumorigenic cancer stem cells (CSCs) generate intermediate progenitors and terminally differentiated cells. Similar to physiological stem cells, CSCs often exhibit resistance to various chemotherapeutic drugs. Recently, we found that oncogenic transformation of circadian clock-defective cells exhibited CSC phenotype cells. Furthermore, oncogenic-transformed circadian clock-defective cells also resisted against the cytotoxicity of chemotherapeutic drugs.
　In this symposium, I would like to summarize our recent findings on the underlying mechanism of development of chemoresistance in circadian clock-defective cells, and also to introduce the chronopharmacological strategy for treatment of malignant tumors.