Heme-thiolate monooxygenase cytochrome P450 1B1, an old dog with many new tricks

Cytochrome P450 CYP1B1 is a heme-thiolate monooxygenase traditionally recognized for its xenobiotic functions and extrahepatic expressions. Recent studies have suggested that CYP1B1 is also expressed in hepatic stellate cells, immune cells, endothelial cells, and fibroblasts within the tumor microenvironment, as well as tumor cells themselves. CYP1B1 is responsible for the metabolism of a wide range of substrates, including xenobiotics such as drugs, environmental chemicals, and endobiotics such as steroids, retinol, and fatty acids. Consequently, CYP1B1 and its associated exogenous and endogenous metabolites have been critically implicated in the pathogenesis of many diseases. Understanding the mode of action of CYP1B1 in different pathophysiological conditions and developing pharmacological inhibitors that allow for systemic or cell type-specific modulation of CYP1B1 may pave the way for novel therapeutic opportunities. This review highlights the significant role of CYP1B1 in maintaining physiological homeostasis and provides a comprehensive discussion of recent advancements in our understanding of CYP1B1's involvement in the pathogenesis of diseases such as fibrosis, cancer, glaucoma, and metabolic disorders. Finally, the review emphasizes the therapeutic potential of targeting CYP1B1 for drug development, particularly in the treatment and prevention of cancers and liver fibrosis. SIGNIFICANCE STATEMENT: CYP1B1 plays a critical role in various physiological processes. Dysregulation or genetic mutations of the gene encoding this enzyme can lead to health complications and may increase the risk of diseases such as cancer and liver fibrosis. In this review, we summarize recent preclinical and clinical evidence that underscores the potential of CYP1B1 as a therapeutic target.