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The use of kinase inhibitors in solid organ transplantation
S Dholakia1, J E Fildes1, P J Friend1
1Nuffield Department of Surgical Science, Oxford Transplant Centre, Churchill Hospital, Oxford, OX3 7LE, UK; The Manchester Collaborative Centre for Inflammation Research (MCCIR), Institute of Inflammation and Repair, Core Technology Facility, University of Manchester, Manchester, M13 9NT, UK.
Introduction:
Despite the efficacy of current immunosuppression regimes used in solid organ transplantation, graft dysfunction, graft lost and antibody-mediated rejection continue to be problematic. As a result, clear attraction in exploiting key potential targets controlled by kinase phosphorylation has led to a number of studies exploring the use of these drugs in transplantation. Aim In this review, we consider the role of tyrosine kinase as a target in transplantation and summarize the relevant studies on kinase inhibitors that have been reported to date.
Methods:
Narrative review of literature from inception to December 2016, using OVID interface searching EMBASE and MEDLINE databases. All studies related to kinase based immunosuppression were examined for clinical relevance with no exclusion criteria. Key ideas were extracted and referenced.
Conclusion:
The higher incidence of infections when using kinase inhibitors is an important consideration, however the number and range inhibitors and their clinical indications are likely to expand, but their exact role in transplantation is yet to be determined.
Insights
Kinase inhibitors show promise in solid organ transplantation, but increased infection risk is a concern. Further research is needed to determine their exact role in improving graft survival and reducing rejection.
Area of Science:
- Immunology
- Pharmacology
- Transplantation Medicine
Background:
- Current immunosuppression in solid organ transplantation faces challenges like graft dysfunction, loss, and antibody-mediated rejection.
- Kinase phosphorylation pathways are increasingly recognized as critical targets for therapeutic intervention in transplantation.
- Tyrosine kinase inhibitors are being explored for their potential to modulate immune responses post-transplant.
Purpose of the Study:
- To review the role of tyrosine kinase as a therapeutic target in solid organ transplantation.
- To summarize existing studies on kinase inhibitors in the context of transplantation.
- To evaluate the clinical relevance and potential applications of kinase inhibitors in transplant medicine.
Main Methods:
- A narrative review of the scientific literature was conducted.
- Searches were performed in EMBASE and MEDLINE databases via the OVID interface.
- Literature from inception to December 2016 was included, with all studies on kinase-based immunosuppression examined for clinical relevance.
Main Results:
- Kinase inhibitors represent a developing area in immunosuppression for solid organ transplantation.
- While promising, the use of kinase inhibitors is associated with a higher incidence of infections.
- The range of available inhibitors and their clinical indications are expanding.
Conclusions:
- Tyrosine kinase inhibitors offer potential new strategies for managing immunosuppression in solid organ transplantation.
- The increased risk of infection associated with kinase inhibitors requires careful consideration and management.
- The precise role and optimal application of kinase inhibitors in transplantation are still under investigation and likely to evolve.