کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5527927 1547896 2017 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Computational drug treatment simulations on projections of dysregulated protein networks derived from the myelodysplastic mutanome match clinical response in patients
ترجمه فارسی عنوان
شبیه سازی محاسبات دارویی بر روی پیش بینی های شبکه های پروتئین کنترل نشده مشتق شده از پاسخ بالینی واکنش مینودال پلاسمایی در بیماران
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی


- Computer modeling of MDS mutanome predicts response to HMAs with 80-100% accuracy.
- Modeling of MDS mutanome revealed biomarkers for drug response.
- Modeling of MDS mutanome unveils resistance pathways to drug therapies.
- Protein network mapping reveals potential targets of drug therapy.

Although the majority of MDS patients fail to achieve clinical improvement to approved therapies, some patients benefit from treatment. Predicting patient response prior to therapy would improve treatment effectiveness, avoid treatment-related adverse events and reduce healthcare costs. Three separate cohorts of MDS patients were used to simulate drug response to lenalidomide alone, hypomethylating agent (HMA) alone, or HMA plus lenalidomide. Utilizing a computational biology program, genomic abnormalities in each patient were used to create an intracellular pathway map that was then used to screen for drug response. In the lenalidomide treated cohort, computer modeling correctly matched clinical responses in 37/46 patients (80%). In the second cohort, 15 HMA patients were modeled and correctly matched to responses in 12 (80%). In the third cohort, computer modeling correctly matched responses in 10/10 patients (100%). This computational biology network approach identified GGH overexpression as a potential resistance factor to HMA treatment and paradoxical activation of beta-catenin (through Csnk1a1 inhibition) as a resistance factor to lenalidomide treatment. We demonstrate that a computational technology is able to map the complexity of the MDS mutanome to simulate and predict drug response. This tool can improve understanding of MDS biology and mechanisms of drug sensitivity and resistance.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Leukemia Research - Volume 52, January 2017, Pages 1-7
نویسندگان
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