Can we utilise the circadian clock to target cancer stem cells?

The 24-hourly circadian clock has been implicated in the regulation of multiple cancer hallmarks and characteristics. Cancer stem cells (CSCs) are a small but significant population of cells within many cancers, characterised by their self-renewal and clonogenic capacities. Increasing evidence points to CSCs having prominent roles in metastasis and drug resistance. However, it remains largely unknown how circadian clocks are involved with CSCs and what implications these interactions have for cancer progression and therapeutics. In this review, we examine the growing evidence on the role of circadian clocks in CSCs and discuss the potential therapeutic implications. This opens up new opportunities to target CSCs through various chronotherapeutic approaches, potentially improving clinical cancer outcomes. We propose different scenarios in which targeting circadian clocks in CSCs or their surrounding microenvironment could be developed into effective therapeutic strategies, including: (1) direct pharmacological targeting of core clock molecules, (2) optimising the timing of systemic anticancer therapies, and (3) targeting the neighbouring cells or systemic factors that influence tumour cells in a circadian-dependent manner.