Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside
Chronic Graft Versus Host Disease (cGVHD) is a major complication of allogeneic stem-cell transplantation (SCT). In many inflammatory fibrotic diseases, such as Systemic Scleroderma (SSc) and cGVHD with fibrotic features, an abnormal activation of transforming growth factor (TGFβ) and platelet-deriv...
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| Language: | English |
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Wiley
2011-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/2011/924954 |
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| author | Jacopo Olivieri Sabrina Coluzzi Imma Attolico Attilio Olivieri |
| author_facet | Jacopo Olivieri Sabrina Coluzzi Imma Attolico Attilio Olivieri |
| author_sort | Jacopo Olivieri |
| collection | DOAJ |
| description | Chronic Graft Versus Host Disease (cGVHD) is a major complication of allogeneic stem-cell transplantation (SCT). In many inflammatory fibrotic diseases, such as Systemic Scleroderma (SSc) and cGVHD with fibrotic features, an abnormal activation of transforming growth factor (TGFβ) and platelet-derived growth factor receptor (PDGF-R) pathways have been observed. Tyrosin Kinase Inhibitors (TKIs), which are currently used for treatment of patients with Chronic Myeloid Leukemia (CML), share potent antifibrotic and antiinflammatory properties, being powerful dual inhibitors of both PDGF-R and TGFβ pathways. Moreover accumulating in vitro data confirm that TKIs, interacting with the TCR and other signalling molecules, carry potent immunomodulatory effects, being involved in both T-cell and B-cell response. Translation to the clinical setting revealed that treatment with Imatinib can achieve encouraging responses in patients with autoimmune diseases and steroid-refractory cGVHD, showing a favourable toxicity profile. While the exact mechanisms leading to such efficacy are still under investigation, use of TKIs in the context of clinical trials should be promoted, aiming to evaluate the biological changes induced in vivo by TKIs and to assess the long term outcome of these patients. Second-generation TKIs, with more favourable toxicity profile are under evaluation in the same setting. |
| format | Article |
| id | doaj-art-934a058e85a64e6cb452442180a3c67b |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-934a058e85a64e6cb452442180a3c67b2025-02-03T01:33:23ZengWileyThe Scientific World Journal1537-744X2011-01-01111908193110.1100/2011/924954924954Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to BedsideJacopo Olivieri0Sabrina Coluzzi1Imma Attolico2Attilio Olivieri3Department of Internal Medicine, Università Politecnica delle Marche, 60121 Ancona, ItalyDepartment of Hematology, Azienda Ospedaliera San Carlo, 85100 Potenza, ItalyDepartment of Hematology, Azienda Ospedaliera San Carlo, 85100 Potenza, ItalyDepartment of Hematology, Università Politecnica delle Marche, 60121 Ancona, ItalyChronic Graft Versus Host Disease (cGVHD) is a major complication of allogeneic stem-cell transplantation (SCT). In many inflammatory fibrotic diseases, such as Systemic Scleroderma (SSc) and cGVHD with fibrotic features, an abnormal activation of transforming growth factor (TGFβ) and platelet-derived growth factor receptor (PDGF-R) pathways have been observed. Tyrosin Kinase Inhibitors (TKIs), which are currently used for treatment of patients with Chronic Myeloid Leukemia (CML), share potent antifibrotic and antiinflammatory properties, being powerful dual inhibitors of both PDGF-R and TGFβ pathways. Moreover accumulating in vitro data confirm that TKIs, interacting with the TCR and other signalling molecules, carry potent immunomodulatory effects, being involved in both T-cell and B-cell response. Translation to the clinical setting revealed that treatment with Imatinib can achieve encouraging responses in patients with autoimmune diseases and steroid-refractory cGVHD, showing a favourable toxicity profile. While the exact mechanisms leading to such efficacy are still under investigation, use of TKIs in the context of clinical trials should be promoted, aiming to evaluate the biological changes induced in vivo by TKIs and to assess the long term outcome of these patients. Second-generation TKIs, with more favourable toxicity profile are under evaluation in the same setting.http://dx.doi.org/10.1100/2011/924954 |
| spellingShingle | Jacopo Olivieri Sabrina Coluzzi Imma Attolico Attilio Olivieri Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside The Scientific World Journal |
| title | Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside |
| title_full | Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside |
| title_fullStr | Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside |
| title_full_unstemmed | Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside |
| title_short | Tirosin Kinase Inhibitors in Chronic Graft versus Host Disease: From Bench to Bedside |
| title_sort | tirosin kinase inhibitors in chronic graft versus host disease from bench to bedside |
| url | http://dx.doi.org/10.1100/2011/924954 |
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