مکانیسم های ملکولی تیروزین کیناز MET در جریان پیشرفت و تهاجم تومور

نوع مقاله : مقاله مروری

نویسندگان

1 کمیته تحقیقات دانشجویی، دانشکده پزشکی، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

2 مرکز تحقیقات ژنتیک پزشکی، دانشگاه علوم پزشکی مشهد، مشهد، ایران.

10.22038/mjms.2025.79037.4549

چکیده

به دلیل اثرات جانبی ناشی از درمان های متداول سرطان همچون شیمی درمانی و رادیوتراپی، امروزه نیاز به یافتن درمان های جدید برای سرطان امری ضروری می باشد. بکارگیری مهارکننده تیروزین کینازها می‌تواند به عنوان یک رویکرد امیدوار کننده برای درمان سرطان باشد. MET بعنوان یک گیرنده تیروزین کیناز دارای نقش بسیار کلیدی در القا تکثیر سلولی، رگزایی، و تحرک سلولی می باشد و از این طریق باعث کمک به القا تشکیل تومور می‌گردد. با توجه به اینکه MET در بسیاری از فرآیندهای فیزیولوژیک و پاتولوژیک شرکت می‌کند، لذا می تواند بعنوان یک هدف درمانی برای مهار بقا سلول‌های سرطانی در نظر گرفته شود. مهارکننده‌های تیروزین کیناز مانند crizotinib، capmatinib وcabozantinib ، می توانند با مهار MET اثربخشی قابل اعتمادی در بهبود بقای بدون پیشرفت بیماری در بیماران سرطانی داشته باشند. آنتی‌بادی‌های مونوکلونال نیز می توانند با اختلال در برهمکنش‌های لیگاند-MET بقای بیماران را بهبود بخشند. با این وجود، مقاومت به مهارکننده MET می‌تواند به دلیل مکانیسم‌های مختلفی اتفاق بیافتد که از جمله آن‌ها تکثیر ژن MET و افزایش بیان آن، جهش نقطه‌ای در ژن MET، و فعال شدن مسیرهای موازی با MET می باشند. در این مقاله، پایگاه های اطلاعاتی Pubmed, Google scholar, Scopus, Web of science تا سال 2024 با کلید واژه های "MET" و "Cancer" مورد بررسی قرار گرفتند. این مقاله می تواند نقش مهمی داشته باشد برای درک بهتر مکانیسم های ملکولی MET در بروز سرطان‌ها و معرفی استراتژی های بهتر برای غلبه بر مقاومت در برابر مهارکننده های MET در بیماران سرطانی.

کلیدواژه‌ها

عنوان مقاله [English]

Molecular mechanisms of MET tyrosine kinase during tumor progression and metastasis

نویسندگان [English]

  • Negin Taghehchian 1
  • Mohmmad Reza Abbaszadegan 2
  • Meysam Moghbeli 2
1 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
2 Medical Genetics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
چکیده [English]

Due to the side effects caused by common cancer treatments such as chemotherapy and radiotherapy, it is required to introduce the novel therapeutic options in cancer patients. In recent years, the molecular orientation of cancer treatment is considered as the most effective approach in personalized cancer medicine. The use of tyrosine kinase inhibitors can be a promising approach for cancer treatment. MET is a receptor tyrosine kinase that has a key role in inducing cell proliferation, angiogenesis, and cell migration, and tumor progression. MET deregulation is associated with poor prognosis and drug resistance in a wide range of cancers. Regarding the role of MET in many physiological and pathological processes, it can be considered as a therapeutic target in tumor cells. Small-molecule tyrosine kinase inhibitors (TKIs) such as crizotinib, capmatinib, and cabozantinib have reliable efficacy to improve progression-free survival in cancer patients by MET inhibition. Monoclonal antibodies also disrupt ligand-MET interactions to improve patient’s survival. However, resistance toward the MET inhibitors can be observed due to the various molecular mechanisms such as MET duplication and up regulation, mutation, and activation of parallel signaling pathways. PubMed, Google Scholar, Scopus, and Web of Science were used for data retrieval until 2024 using the “MET” and "cancer" keywords. This review has an important role to clarify the molecular biology of MET during tumor progression to introduce novel efficient therapeutic strategies to overcome resistance toward MET inhibitors among cancer patients.

کلیدواژه‌ها [English]

  • MET
  • Tyrosine kinase
  • Cancer
  • Drug resistance

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مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد
دوره 68، شماره 6
بهمن-اسفند1404
بهمن و اسفند 1404
صفحه 1801-1814

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