کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5534394 1551126 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Accelerating glioblastoma drug discovery: Convergence of patient-derived models, genome editing and phenotypic screening
ترجمه فارسی عنوان
کشف داروهای گلیوبلاستوما: همگرایی مدل های مبتنی بر بیمار، ویرایش ژنوم و غربالگری فنوتیپیک
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
چکیده انگلیسی


- A discussion of the types of normal neural stem and progenitor cells and how these can be deployed to study glioblastoma.
- A discussion of the potential applications of CRISPR/Cas based genome editing for the glioblastoma drug discovery pipeline.
- A discussion of the power of image-based chemical screens for glioblastoma.

Patients diagnosed with glioblastoma (GBM) continue to face a bleak prognosis. It is critical that new effective therapeutic strategies are developed. GBM stem cells have molecular hallmarks of neural stem and progenitor cells and it is possible to propagate both non-transformed normal neural stem cells and GBM stem cells, in defined, feeder-free, adherent culture. These primary stem cell lines provide an experimental model that is ideally suited to cell-based drug discovery or genetic screens in order to identify tumour-specific vulnerabilities. For many solid tumours, including GBM, the genetic disruptions that drive tumour initiation and growth have now been catalogued. CRISPR/Cas-based genome editing technologies have recently emerged, transforming our ability to functionally annotate the human genome. Genome editing opens prospects for engineering precise genetic changes in normal and GBM-derived neural stem cells, which will provide more defined and reliable genetic models, with critical matched pairs of isogenic cell lines. Generation of more complex alleles such as knock in tags or fluorescent reporters is also now possible. These new cellular models can be deployed in cell-based phenotypic drug discovery (PDD). Here we discuss the convergence of these advanced technologies (iPS cells, neural stem cell culture, genome editing and high content phenotypic screening) and how they herald a new era in human cellular genetics that should have a major impact in accelerating glioblastoma drug discovery.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 80, April 2017, Pages 198-207
نویسندگان
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