کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6190424 1601113 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Personalized therapy for hepatocellular carcinoma: Where are we now?
ترجمه فارسی عنوان
درمان شخصی برای کارسینوم سلول های کبدی: اکنون ما کجا هستیم؟
کلمات کلیدی
نئوپلاسم کبدی، دارو، بیومارکر، درمان هدفمند،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی تومور شناسی
چکیده انگلیسی


- Subgroup analyses of several clinical trials on HCC suggested that targeted agents had different efficacy in various populations.
- Recent advances in next generation sequencing revealed high inter-patient heterogeneity in HCC in terms of genetic mutations.
- Molecular enrichment strategy may be adopted for drug testing in HCC, which could be paved by advances in liquid biopsy and concepts of trial design.

Following the approval of sorafenib, a large number of molecular targeted agents have been tested clinically for advanced hepatocellular carcinoma (HCC), but all have failed to demonstrate significant efficacy in clinical trials. Multiple reasons for this phenomenon have been discussed in the literature, with one reason being the lack of patient selection on the basis of molecular profile in clinical trials. The concept of drug testing in selected populations has been recently suggested by retrospective analyses of HCC clinical trials in which a particular subgroup of patients, either enriched by clinical factors or by tissue biomarkers, derived more benefits from the novel drug. In addition, recent advances in genomic medicine have enhanced the understanding of genetic and epigenetic events occurring in HCC, raising the possibility of personalizing targeted agents in accordance with the genetic make-up of the tumors. The development of 'personalized' treatment for HCC is, however, hindered by the lack of fresh biopsy of advanced HCC, the low incidence of genetic driver mutations in HCC and the tumor heterogeneity. These limitations may be overcome by sequencing cell-free DNA in plasma, frequently known as liquid biopsy, and revolution in the concept of the design of clinical trials. In this review article, we aim to: (1) give a summary of the recent sequencing results of HCC and the related implications for drug development; (2) highlight potential individual targeted agents and existing research on biomarker selection in clinical trials; and (3) discuss future directions, including the potential of liquid biopsy and umbrella clinical trials, to enhance personalized drug testing for HCC.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cancer Treatment Reviews - Volume 45, April 2016, Pages 77-86
نویسندگان
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