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Vol. 12. Issue 2.
Pages 91-99 (March - April 2016)
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Vol. 12. Issue 2.
Pages 91-99 (March - April 2016)
Review Article
DOI: 10.1016/j.reumae.2015.06.003
Protein-kinase Inhibitors: A New Treatment Pathway for Autoimmune and Inflammatory Diseases?
Los inhibidores de las proteínas-cinasas en enfermedades autoinmunes e inflamatorias: presente y futuro de nuevas dianas terapéuticas
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Diana Hernández-Flórez, Lara Valor
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lvalor.hgugm@salud.madrid.org

Corresponding author.
Servicio de Reumatología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Table 1. Abbreviations.
Table 2. Protein Kinase Inhibitors Evaluated for the Treatment of Autoimmune and Inflammatory Diseases.
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Abstract

Although advances in biological medicine have seen significant progress in the treatment of autoimmune and inflammatory disease, many patients do not experience a satisfactory response. Hence, there are two challenges facing the medical research community. The first is to continue development in the field of existing biological therapies, such as monoclonal antibodies. The second is to open new frontiers of research and explore treatment alternatives for non-responders to other therapies. Attention has increasingly turned to the therapeutic potential of small molecule weight kinase inhibitors (SMKIs), currently used extensively in oncology and hematology. Initial research into the therapeutic value of SMKIs for autoimmune and inflammatory diseases has been encouraging. SMKIs are taken orally, which reduces cost for the health provider, and could increase compliance for the patient. This is why research is now focusing increasingly on SMKIs as a new generation line of treatment in these diseases. Tofacitinib, an inhibitor of Janus-kinase, is currently the only drug approved for the treatment of rheumatoid arthritis by FDA. However, much more needs to be done to understand the intracellular signaling pathways and how these might affect disease progression before solid conclusions can be drawn.

Keywords:
Protein-kinase
Tyrosine-kinase
Kinase inhibitors
Intracellular signaling
Autoimmunity
Inflammation
Tofacitinib
Resumen

Pese a los avances terapéuticos en las enfermedades autoinmunes e inflamatorias, muchos pacientes no logran un control adecuado de la enfermedad. De ahí la necesidad de optimizar el uso de las terapias biológicas y de explorar nuevas opciones terapéuticas. La disponibilidad de fármacos que inhiben proteínas-cinasas ya es una realidad en especialidades como oncología y hematología, donde los resultados asociados a la evolución clínica de la enfermedad han sido prometedores. La principal ventaja de estos fármacos es la administración oral, que podría favorecer la adherencia del paciente y reducir los costes asociados al tratamiento. Tofacitinib, inhibidor de tirosinas-cinasas, actualmente es el único fármaco de esta categoría aprobado para el tratamiento de la artritis reumatoide por la FDA. Estas dianas terapéuticas son evaluadas actualmente en diversas enfermedades autoinmunes e inflamatorias. Sin embargo, el conocimiento y la comprensión de las vías de señalización intracelular siguen siendo limitados, persistiendo dudas en cuanto al mecanismo de acción, la eficacia y los posibles efectos secundarios asociados al uso de estos nuevos fármacos.

Palabras clave:
Proteínas-cinasas
Tirosinas-cinasas
Inhibidores de las tirosinas-cinasas
Vías de señalización intracelular
Autoinmunidad
Inflamación
Tofacitinib

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