Calcineurin inhibitor (CNI)-associated skin cancers: New insights on exploring mechanisms by which CNIs downregulate DNA repair machinery |
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Authors: | Adaku C. Ume Jennifer M. Pugh Michael G. Kemp Clintoria R. Williams |
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Affiliation: | 1. Department of Neuroscience, Cell Biology & Physiology, College of Science and Mathematics, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA;2. Department of Pharmacology & Toxicology, Wright State University Boonshoft School of Medicine, Dayton, Ohio, USA |
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Abstract: | The use of the calcineurin inhibitors (CNI) cyclosporine (CsA) and tacrolimus remains a cornerstone in post-transplantation immunosuppression. Although these immunosuppressive agents have revolutionized the field of transplantation medicine, its increased skin cancer risk poses a major concern. A key contributor to this phenomenon is a reduced capacity to repair DNA damage caused by exposure to ultraviolet (UV) wavelengths of sunlight. CNIs decrease DNA repair by mechanisms that remain to be fully explored. Though CsA is known to decrease the abundance of key DNA repair enzymes, less is known about how tacrolimus yields this effect. CNIs hold the capacity to inhibit both of the main catalytic calcineurin isoforms (CnAα and CnAβ). However, it is unknown which isoform regulates UV-induced DNA repair, which is the focus of this review. It is with hope that this insight spurs investigative efforts that conclusively addresses these gaps in knowledge. Additionally, this research also raises the possibility that newer CNIs can be developed that effectively blunt the immune response while mitigating the incidence of skin cancers with immunosuppression. |
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Keywords: | active calcineurin isoforms calcineurin inhibitors DNA repair skin cancer ultraviolet light |
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