کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8436425 1546826 2018 80 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Host genetic profiling to increase drug safety in colorectal cancer from discovery to implementation
ترجمه فارسی عنوان
پروفایل ژنتیکی میزبان برای افزایش ایمنی مواد در سرطان کولورکتال از کشف تا پیاده سازی
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
چکیده انگلیسی
Adverse events affect the pharmacological treatment of approximately 90% of colorectal cancer (CRC) patients at any stage of the disease. Chemotherapy including fluoropyrimidines, irinotecan, and oxaliplatin is the cornerstone of the pharmacological treatment of CRC. The introduction of novel targeted agents, as anti-EGFR (i.e. cetuximab, panitumumab) and antiangiogenic (i.e. bevacizumab, ziv-aflibercept, regorafenib, and ramucirumab) molecules, into the oncologist's toolbox has led to significant improvements in the life expectancy of advanced CRC patients, but with a substantial increase in toxicity burden. In this respect, pharmacogenomics has largely been applied to the personalization of CRC chemotherapy, focusing mainly on the study of inhered polymorphisms in genes encoding phase I and II enzymes, ATP-binding cassette (ABC)/solute carrier (SLC) membrane transporters, proteins involved in DNA repair, folate pathway and immune response. These research efforts have led to the identification of some validated genetic markers of chemotherapy toxicity, for fluoropyrimidines and irinotecan. No validated genetic determinants of oxaliplatin-specific toxicity, as peripheral neuropathy, has thus far been established. The contribution of host genetic markers in predicting the toxicity associated with novel targeted agents' administration is still controversial due to the heterogeneity of published data. Pharmacogenomics guidelines have been published by some international scientific consortia such as the Clinical Pharmacogenomics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG) strongly suggesting a pre-treatment dose adjustment of irinotecan based on UGT1A1*28 genotype and of fluoropyrimidines based on some DPYD genetic variants, to increase treatment safety. However, these recommendations are still poorly applied at the patient's bedside. Several ongoing projects in the U.S. and Europe are currently evaluating how pharmacogenomics can be implemented successfully in daily clinical practice. The majority of drug-related adverse events are still unexplained, and a great deal of ongoing research is aimed at improving knowledge of the role of pharmacogenomics in increasing treatment safety. In this review, the issue of pre-treatment identification of CRC patients at risk of toxicity via the analysis of patients' genetic profiles is addressed. Available pharmacogenomics guidelines with ongoing efforts to implement them in clinical practice and new exploratory markers for clinical validation are described.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Drug Resistance Updates - Volume 39, July 2018, Pages 18-40
نویسندگان
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