کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5530249 1401724 2016 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Establishing proof of mechanism: Assessing target modulation in early-phase clinical trials
ترجمه فارسی عنوان
ایجاد اثبات مکانیزم: ارزیابی مدولاسیون هدف در مطالعات بالینی اولیه فاز
کلمات کلیدی
فارماکودینامیک، بیومارکرها، بیوپسی بافت های جایگزین، فاز اول، ارزیابی مواد مخدر،
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی
Since modulation of the putative target and the observed anti-tumor effects form the basis for the clinical development of a molecularly targeted therapy, early-phase clinical trials should be designed to demonstrate proof-of-mechanism in tissues of interest. In addition to establishing safety and the maximum tolerated dose, first-in-human clinical trials should be designed to demonstrate target modulation, define the proposed mechanism of action, and evaluate pharmacokinetic-pharmacodynamic relationships of a new anti-cancer agent. Assessing target modulation in paired tumor biopsies in patients with solid tumors presents multiple challenges, including procedural issues such as patient safety, ethical considerations, and logistics of sample handling and processing. In addition, the availability of qualified biomarker assay technologies, resources to conduct such studies, and real-time analysis of samples to detect inter-species differences that may affect the determination of optimal sampling time points must be taken into account. This article provides a discussion of the challenges that confront the practical application of pharmacodynamic studies in early-phase clinical trials of anti-cancer agents.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Seminars in Oncology - Volume 43, Issue 4, August 2016, Pages 446-452
نویسندگان
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