Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair

@article{Kuschal2012SkinCI,
  title={Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair},
  author={C. Kuschal and K. Thoms and S. Schubert and A. Sch{\"a}fer and L. Boeckmann and M. Sch{\"o}n and S. Emmert},
  journal={Experimental Dermatology},
  year={2012},
  volume={21}
}
Abstract:  UV‐induced skin cancers comprise a major problem in organ transplant recipients (OTRs). Cyclosporin A, a calcineurin inhibitor, is used as a standard immunosuppressant and clearly increases the skin cancer risk. Azathioprine does not appear to result in such an increase in skin cancer risk, and mTOR inhibitors are associated with an even lesser skin cancer risk. The underlying molecular mechanisms of these clinically important differences among immunosuppressants are still unclear… Expand
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TLDR
In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and siro Limus tolerance was satisfactory. Expand
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TLDR
Clinical efforts aimed at reduction in skin cancers in this high-risk population include increased education and surveillance, aggressive treatment of skin cancers and pre-cancers, changes to immunosuppressive regimens, and retinoid chemoprevention. Expand
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TLDR
It has to be emphasized that an interdisciplinary approach, coordinated by the transplant center, that includes regular skin examinations by a dermatologist is needed to ensure the best care for the OTRs. Expand
Epidemiologic perspectives on immunosuppressed populations and the immunosurveillance and immunocontainment of cancer
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  • Medicine
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  • 2019
TLDR
These epidemiologic observations suggest that there are 2 distinct immune selection processes in humans: immunosurveillance directed against premalignant cells before cancer diagnosis (most relevant for preventing virus‐related cancers), and “immunocontainment” directed against established cancers. Expand
Systemic glucocorticoid use and early-onset basal cell carcinoma.
TLDR
While short-term steroid use is not known to have any lasting impact on immune function, transient immune suppression from systemic steroid use could impact BCC risk, especially in those with high ultraviolet radiation exposure, which may itself induce local immune suppression. Expand
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References

SHOWING 1-10 OF 83 REFERENCES
Immunosuppressants and Skin Cancer in Transplant Patients: Focus on Rapamycin
TLDR
Data suggest that rapamycin could have a protective effect against skin cancer, and new immunosuppressive strategies for transplant patients with skin cancer are not only based on minimizing immunOSuppression. Expand
More epidermal p53 patches adjacent to skin carcinomas in renal transplant recipients than in immunocompetent patients: the role of azathioprine
TLDR
Investigating whether this drug could increase UV‐induced p53 patches by immunosuppression found no increase, and DNA repair was investigated by ascertaining the effect of azathioprine on unscheduled DNA synthesis (UDS) in UV‐irradiated human keratinocytes. Expand
Molecular Concepts of Virus Infections Causing Skin Cancer in Organ Transplant Recipients
  • I. Nindl, F. Rösl
  • Medicine
  • American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
  • 2008
TLDR
A rodent model system useful to examine future strategies in preventing skin tumor formation in immunosuppressed OTR is described and virus‐induced transformation with special emphasis on the function of HPV as an indirect and HHV‐8 as direct carcinogen in the development of NMSC and Kaposi sarcoma. Expand
Use of proliferation signal inhibitors in non-melanoma skin cancer following renal transplantation
TLDR
The effect of conversion to PSIs in 53 renal transplant recipients developing NMSC after transplantation was generally well tolerated with minimal adverse events reported, and data suggest that conversion from CNIs to PSI may be useful in the management of N MSC following renal transplantation. Expand
Cyclosporine A suppresses keratinocyte cell death through MPTP inhibition in a model for skin cancer in organ transplant recipients.
TLDR
It is suggested that CsA may promote skin cancer in transplant patients by allowing keratinocyte survival under conditions of increased genotoxic stress. Expand
Expression of DNA mismatch repair proteins and MSH2 polymorphisms in nonmelanoma skin cancers of organ transplant recipients
TLDR
Treatment with azathioprine, commonly used in post‐transplant immunosuppressive regimens, results in incorporation of 6‐thioguanine (6‐TG) into DNA, which confers a survival advantage on MMR‐defective cells, which are hypermutable and may therefore contribute to azithioprine‐related nonmelanoma skin cancer, a phenomenon previously demonstrated in transplant‐associated sebaceous carcinomas. Expand
Calcineurin inhibitors decrease DNA repair and apoptosis in human keratinocytes following ultraviolet B irradiation.
TLDR
The data suggest that the increased risk of skin cancer observed in organ-transplant patients may be as a result of not only systemic immune suppression but also the local inhibition of DNA repair and apoptosis in skin by calcineurin inhibitors. Expand
Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients.
TLDR
Triple therapy was associated with impaired PBMC DNA repair and increased cancer incidence and CsA was responsible in large part for the reduction in DNA repair ability found in the in vitro and in vivo studies. Expand
Skin cancer in kidney and heart transplant recipients and different long-term immunosuppressive therapy regimens.
TLDR
The risk of cutaneous SCC, malignant melanoma, Kaposi's sarcoma, and lip SCC is increased in kidney and heart transplant recipients, and the risk is related to the degree of immunosuppression caused by long-term Immunosuppressive therapy. Expand
Skin Cancer in Organ Transplant Recipients—Where Do We Stand Today?
TLDR
Although the threshold of skin cancer necessitating revision of immunosuppression is debated, this measure should be envisaged at the occurrence of the first SCC, or in case of multiple non‐SCC NMSC. Expand
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