Nuclear receptors Liver X Receptor-α (LXRα; NR1H3) and Liver X Receptor-β (LXRβ; NR1H2) are considered master regulators of lipid homeostasis. During the last couple of decades, their pivotal roles in several physiological and pathological processes ranging from energy supply, immunity, cardiovascular and neurodegenerative disorders, and cancer have been highlighted. In this review, the main results achieved during the years about the understanding of LXRs involvement in cancer have been collected according to the small-molecule chemical probe used. Remarkably, all the probes, albeit different in structure and biological properties, have well evidenced the antitumoral activity arising from LXRs modulation pointing out the high potential of LXRs targeting in clinical treatment of cancer
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