Targeted Cancer Therapy: Tyrosine Kinase Inhibitors

Year 2022, Volume: 31 Issue: 2, 78 - 81, 30.06.2022

Serhan Küpeli

https://doi.org/10.17827/aktd.1081737

Abstract

Cancers generally contain multiple genetic and epigenetic abnormalities, but several key genes maintain the malignant phenotype and cellular survival. Tyrosine kinases are often involved in the cellular response with growth factors, cytokines, and hormones. These molecules are responsible for tumor growth by various mechanisms. It is thought that tyrosine kinase inhibitors may have a wide range of therapeutic efficacy. Significant response rates could not be obtained in phase 1 studies with any of the agents in monotherapy, and other options are being investigated by administering high doses in short periods and combining drugs that may affect different pathways.

Keywords

Tyrosine kinase inhibitors, cancer, targeted therapy

Kanserde Hedefe Yönelik Tedavi: Tirozin Kinaz İnhibitörleri

Abstract

Kanserler genel olarak çoklu genetik ve epigenetik anormallikler içermekte fakat birkaç anahtar gen sayesinde malign fenotip ve hücresel sağkalımın devamlılığı sağlanmaktadır. Tirozin kinazlar sıklıkla büyüme faktörleri, sitokinler ve hormonlar ile hücresel cevapta rol oynarlar. Bu moleküller tümör büyümesinden çeşitli mekanizmalarla sorumludurlar. Tirozin kinaz inhibitörlerin geniş bir terapötik etkinliğinin olabileceği düşünülmektedir. Tek ilaçla yapılan tedavide bu inhibitörlerin hiçbiri ile faz 1 çalışmalarda önemli cevap oranları elde edilememiş olup yüksek dozların kısa sürelerde verilmesi ve değişik yolaklara etkili olabilecek ilaçların kombine edilmesi gibi diğer seçenekler araştırılmaktadır.

Keywords

Tirozin kinaz inhibitörleri, kanser, hedefe yönelik tedavi

References

• 1. Maruyama IN. Mechanisms of activation of receptor tyrosine kinases: Monomers or dimers. Cell. 2014;3:304-330.
• 2. Posner I, Engel M, Gazit A, Levitzki A. Kinetics of inhibition by tyrphostins of the tyrosine kinase activity of the epidermal growth factor receptor and analysis by a new computer program. Molecular Pharmacology. 1994;45:673-683.
• 3.FDA Approved Drugs for Oncology. 2018. Available from: www.centerwatch.com/druginformation/fda-approved-drugs/therapeutic-area/12/oncology.
• 4. Sequist LV. Second-generation epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. The Oncologist. 2007;12:325-330.
• 5. Sillaber C, Mayerhofer M, Agis H, Sagaster V, Mannhalter C, Sperr WR et al. Chronic myeloid leukemia: Pathophysiology, diagnostic parameters, and current treatment concepts. Wiener Klinische Wochenschrift. 2003;115:485-504.
• 6. Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. The New England Journal of Medicine. 2003;349:1423-1432.
• 7. Deininger M, O'Brien SG, Guilhot F, Goldman JM, Hochhaus A, Hughes TP et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood. 2009;114:1126.
• 8. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. Journal of Clinical Oncology. 2003;21:4342-4349.
• 9. Kerob D, Porcher R, Vérola O, Dalle S, Maubec E, Aubin F et al. Imatinib mesylate as a preoperative therapy in dermatofibrosarcoma: Results of a multicenter phase II study on 25 patients. Clinical Cancer Research. 2010;16:3288-3295.
• 10. Ha HT, Lee JS, Urba S, Koenig RJ, Sisson J, Giordano T et al. A phase II study of imatinib in patients with advanced anaplastic thyroid cancer. Thyroid. 2010;20:975-980.
• 11. Aguilera DG, Tsimberidou AM. Dasatinib in chronic myeloid leukemia: A review. Therapeutics and Clinical Risk Management. 2009;5:281-289.
• 12. Kwak JY, Kim H, Kim JA, Do YR, Kim HJ, Park JS et al. Efficacy and safety of radotinib compared with imatinib in newly diagnosed chronic phase chronic myeloid leukemia patients: 12 months result of phase 3 clinical trial. Blood. 2015;126:476.
• 13. Cortes JE, Kim DW, Pinilla-Ibarz J, le Coutre PD, Paquette R, Chuah C et al. Ponatinib efficacy and safety in Philadelphia chromosomepositive leukemia: Final 5-year results of the phase 2 PACE trial. Blood. 2018;132:393-404. 14. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: Epidemiology, risk factors, treatment, and survivorship. Mayo Clinic Proceedings. 2008;83:584-594.
• 15. Zhang W, Wei Y, Yu D, Xu J, Peng J. Gefitinib provides similar effectiveness and improved safety than erlotinib for advanced nonsmall cell lung cancer: A meta-analysis. Medicine. 2018;97:e0460.
• 16. Soria J-C, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH et al. Osimertinib in untreated EGFR-mutated advanced non-small-cell lung cancer. The New England Journal of Medicine. 2018;378:113-125.
• 17. Zhang HL, Sheng XN, Li XS, Wang HK, Chi ZH, He ZS et al. Sorafenib versus sunitinib as first-line treatment agents in Chinese patients with metastatic renal cell carcinoma: The largest multicenter retrospective analysis of survival and prognostic factors. BMC Cancer. 2017;17:16.
• 18. Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): An international, multicentre, randomised, placebocontrolled, phase 3 trial. The Lancet. 2013;381:303-312.
• 19. Padula WV, Larson RA, Dusetzina SB, Apperley JF, Hehlmann R, Baccarani M et al. Cost-effectiveness of tyrosine kinase inhibitor treatment strategies for chronic myeloid leukemia in chronic phase after generic entry of imatinib in the United States. Journal of the National Cancer Institute. 2016;108:djw003.