کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5557698 | 1560932 | 2017 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibitors of cyclin-dependent kinases as cancer therapeutics
ترجمه فارسی عنوان
مهار کننده های کیناز وابسته به سیکلین به عنوان درمان سرطان
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کلمات کلیدی
PI3KAMLCAKDSIFCLLDLTNELFLRPCDKCDK-activating kinase - CDK فعال کینازMAPK - MAPKPFs - PF هاPhosphatidylinositol-4,5-bisphosphate 3-kinase - Phosphatidylinositol-4،5-bisphosphate 3-kinaseInhibitor - بازدارندهProgression free survival - بقای آزاد شدن پیشرفتdose-limiting toxicities - دوز محدود کننده سمیتTranscription - رونویسیacute myeloid leukemia - لوسمی حاد میلوئیدی یا به اختصار AMLChronic lymphocytic leukemia - لوسمی مزمن لنفوئیدیretinoblastoma protein - پروتئین رتینوبلاستوماmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenCell cycle - چرخه سلولیcyclin-dependent kinases - کیناز وابسته به سیکلینcyclin-dependent kinase - کییناز وابسته به سیکلینEstrogen receptor - گیرنده استروژن
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
چکیده انگلیسی
Over the past two decades there has been a great deal of interest in the development of inhibitors of the cyclin-dependent kinases (CDKs). This attention initially stemmed from observations that different CDK isoforms have key roles in cancer cell proliferation through loss of regulation of the cell cycle, a hallmark feature of cancer. CDKs have now been shown to regulate other processes, particularly various aspects of transcription. The early non-selective CDK inhibitors exhibited considerable toxicity and proved to be insufficiently active in most cancers. The lack of patient selection biomarkers and an absence of understanding of the inhibitory profile required for efficacy hampered the development of these inhibitors. However, the advent of potent isoform-selective inhibitors with accompanying biomarkers has re-ignited interest. Palbociclib, a selective CDK4/6 inhibitor, is now approved for the treatment of ERÂ +/HER2- advanced breast cancer. Current developments in the field include the identification of potent and selective inhibitors of the transcriptional CDKs; these include tool compounds that have allowed exploration of individual CDKs as cancer targets and the determination of their potential therapeutic windows. Biomarkers that allow the selection of patients likely to respond are now being discovered. Drug resistance has emerged as a major hurdle in the clinic for most protein kinase inhibitors and resistance mechanism are beginning to be identified for CDK inhibitors. This suggests that the selective inhibitors may be best used combined with standard of care or other molecularly targeted agents now in development rather than in isolation as monotherapies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Pharmacology & Therapeutics - Volume 173, May 2017, Pages 83-105
Journal: Pharmacology & Therapeutics - Volume 173, May 2017, Pages 83-105
نویسندگان
Steven R. Whittaker, Aurélie Mallinger, Paul Workman, Paul A. Clarke,