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Ruxolitinib ve etki mekanizmaları

Year 2016, Volume: 2 Issue: 2, 153 - 157, 01.06.2016

Bakiye Göker Bağca Çığır Biray Avcı

Abstract

Ruxolitinib JAK1 ve JAK2 tirozin kinazlarının inhibitörüdür. Jakafi adıyla piyasaya sürülen ruxolitinib, miyelofibroz tedavisinde onaylanan ilk kimyasalajan olarak 2011 yılından beri kullanılmaktadır. Miyeloproliferatif neoplazmlar (MPN) Philadelphia kromozom (Ph) pozitif ve negatif hastalıkları içerir.2001 yılında imatinib tirozin kinazının geliştirilmesinden bu yana Ph+ kronik miyeloid lösemi tedavisinde tirozin kinaz inhibitörlerine odaklanılmıştır.Direnç gelişimine bağlı olarak yeni nesil tirozin kinaz inhibitörleri geliştirilmiş ve kullanılmıştır. Bunun tersine Ph- MPN’lerde hedefli tedavi dahaaz anlaşılmış güncel bir konudur. Ph-MPN’ler genellikle JAK-STAT yolağının mutasyonlarından kaynaklanır. Bu derlemede hem Ph+ hem de Ph-MPN’lerde en güncel tirozin kinaz inhibitörü olan ruxolitinib ile oluşturulabilecek hedefli tedavi seçenekleri incelenmiştir.

Keywords

mekanizmalar miyeloproliferatif neoplazmlar ruxolitinib

References

  • Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292-302.
  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937-51.
  • Mesa RA, Shields A, Hare T, Erickson-Viitanen S, Sun W, Sarlis NJ, et al. Progressive burden of myelofibrosis in untreated patients: assessment of patient-reported outcomes in patients randomized to placebo in the COMFORT-I study. Leuk Res 2013;37:911-6.
  • Mesa RA, Kantarjian H, Tefferi A, Dueck A, Levy R, Vaddi K, et al. Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer 2011;117:4869-77.
  • Mascarenhas J, Mughal TI, Verstovsek S. Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. Curr Med Chem 2012;19:4399-413.
  • Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc 2011;86:1188-91.
  • Tefferi A. How I treat myelofibrosis. Blood 2011;117:3494-504.
  • Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010;115:1703-8.
  • Tefferi A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia 2008;22:3-13.
  • Seavey MM, Dobrzanski P. The many faces of Janus kinase. Biochem Pharmacol 2012;83:1136-45.
  • Rawlings JS, Rosler KM, Harrison DA. The JAK/ STAT signaling pathway. J Cell Sci 2004;117:1281-3.
  • Nicolas CS, Amici M, Bortolotto ZA, Doherty A, Csaba Z, Fafouri A, et al. The role of JAK-STAT signaling within the CNS. JAKSTAT 2013;2:22925.
  • Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol 2011;7:1035-43.
  • Yang LP, Keating GM. Ruxolitinib: in the treatment of myelofibrosis. Drugs 2012;72:2117-27.
  • Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res 2012;18:3008-14.
  • Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115:3109-17.
  • Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-27.
  • Pattison MJ, MacKenzie KF, Elcombe SE, Arthur JS. IFNb autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages. FEBS Lett 2013;587:1496-503.
  • Fridman JS, Scherle PA, Collins R, Burn T, Neilan CL, Hertel D, et al. Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J Invest Dermatol 2011;131:1838-44.
  • Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 2012;67:658-64.

Year 2016, Volume: 2 Issue: 2, 153 - 157, 01.06.2016

Bakiye Göker Bağca Çığır Biray Avcı

Abstract

References

  • Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002;100:2292-302.
  • Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937-51.
  • Mesa RA, Shields A, Hare T, Erickson-Viitanen S, Sun W, Sarlis NJ, et al. Progressive burden of myelofibrosis in untreated patients: assessment of patient-reported outcomes in patients randomized to placebo in the COMFORT-I study. Leuk Res 2013;37:911-6.
  • Mesa RA, Kantarjian H, Tefferi A, Dueck A, Levy R, Vaddi K, et al. Evaluating the serial use of the Myelofibrosis Symptom Assessment Form for measuring symptomatic improvement: performance in 87 myelofibrosis patients on a JAK1 and JAK2 inhibitor (INCB018424) clinical trial. Cancer 2011;117:4869-77.
  • Mascarenhas J, Mughal TI, Verstovsek S. Biology and clinical management of myeloproliferative neoplasms and development of the JAK inhibitor ruxolitinib. Curr Med Chem 2012;19:4399-413.
  • Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc 2011;86:1188-91.
  • Tefferi A. How I treat myelofibrosis. Blood 2011;117:3494-504.
  • Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, et al. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood 2010;115:1703-8.
  • Tefferi A. The history of myeloproliferative disorders: before and after Dameshek. Leukemia 2008;22:3-13.
  • Seavey MM, Dobrzanski P. The many faces of Janus kinase. Biochem Pharmacol 2012;83:1136-45.
  • Rawlings JS, Rosler KM, Harrison DA. The JAK/ STAT signaling pathway. J Cell Sci 2004;117:1281-3.
  • Nicolas CS, Amici M, Bortolotto ZA, Doherty A, Csaba Z, Fafouri A, et al. The role of JAK-STAT signaling within the CNS. JAKSTAT 2013;2:22925.
  • Ostojic A, Vrhovac R, Verstovsek S. Ruxolitinib: a new JAK1/2 inhibitor that offers promising options for treatment of myelofibrosis. Future Oncol 2011;7:1035-43.
  • Yang LP, Keating GM. Ruxolitinib: in the treatment of myelofibrosis. Drugs 2012;72:2117-27.
  • Mascarenhas J, Hoffman R. Ruxolitinib: the first FDA approved therapy for the treatment of myelofibrosis. Clin Cancer Res 2012;18:3008-14.
  • Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, et al. Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood 2010;115:3109-17.
  • Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA, et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010;363:1117-27.
  • Pattison MJ, MacKenzie KF, Elcombe SE, Arthur JS. IFNb autocrine feedback is required to sustain TLR induced production of MCP-1 in macrophages. FEBS Lett 2013;587:1496-503.
  • Fridman JS, Scherle PA, Collins R, Burn T, Neilan CL, Hertel D, et al. Preclinical evaluation of local JAK1 and JAK2 inhibition in cutaneous inflammation. J Invest Dermatol 2011;131:1838-44.
  • Punwani N, Scherle P, Flores R, Shi J, Liang J, Yeleswaram S, et al. Preliminary clinical activity of a topical JAK1/2 inhibitor in the treatment of psoriasis. J Am Acad Dermatol 2012;67:658-64.
There are 20 citations in total.

Details

Journal Section Review
Authors

Bakiye Göker Bağca This is me

Çığır Biray Avcı This is me

Publication Date June 1, 2016
Published in Issue Year 2016 Volume: 2 Issue: 2

Cite

APA Göker Bağca, B., & Avcı, Ç. B. (2016). Ruxolitinib ve etki mekanizmaları. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, 2(2), 153-157. https://doi.org/10.5606/fng.btd.2016.028
AMA Göker Bağca B, Avcı ÇB. Ruxolitinib ve etki mekanizmaları. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. June 2016;2(2):153-157. doi:10.5606/fng.btd.2016.028
Chicago Göker Bağca, Bakiye, and Çığır Biray Avcı. “Ruxolitinib Ve Etki Mekanizmaları”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2, no. 2 (June 2016): 153-57. https://doi.org/10.5606/fng.btd.2016.028.
EndNote Göker Bağca B, Avcı ÇB (June 1, 2016) Ruxolitinib ve etki mekanizmaları. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2 2 153–157.
IEEE B. Göker Bağca and Ç. B. Avcı, “Ruxolitinib ve etki mekanizmaları”, İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, vol. 2, no. 2, pp. 153–157, 2016, doi: 10.5606/fng.btd.2016.028.
ISNAD Göker Bağca, Bakiye - Avcı, Çığır Biray. “Ruxolitinib Ve Etki Mekanizmaları”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi 2/2 (June 2016), 153-157. https://doi.org/10.5606/fng.btd.2016.028.
JAMA Göker Bağca B, Avcı ÇB. Ruxolitinib ve etki mekanizmaları. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2016;2:153–157.
MLA Göker Bağca, Bakiye and Çığır Biray Avcı. “Ruxolitinib Ve Etki Mekanizmaları”. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi, vol. 2, no. 2, 2016, pp. 153-7, doi:10.5606/fng.btd.2016.028.
Vancouver Göker Bağca B, Avcı ÇB. Ruxolitinib ve etki mekanizmaları. İstanbul Bilim Üniversitesi Florence Nightingale Tıp Dergisi. 2016;2(2):153-7.
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