Search results for "pharmacogenetics"
showing 10 items of 90 documents
Evolution of Therapy Decision-Making Process for Advanced Non-Small Cell Lung Cancer
2010
Advanced non-small cell lung cancer remains a lethal disease with poor prognosis. In the last decades results of systemic chemotherapy have reached a disappointing plateau without significant differences between the most widely employed third-generation regimens. Recent scientific evidence has shed new light on the management of advanced non-small cell lung cancer, especially for the important role of histological definition in therapy-planning process. The results of new biologic agents are also reported as are the promising data on pharmacogenomic-guided treatment.
Association of candidate pharmacogenetic markers with platinum-induced ototoxicity
2020
Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase (TPMT) is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers. 1,112 pediatric cancer survivors who had provided biomaterial for genotyping were screened for participation in the pharmacogenetic association study. 900 participants qualified for inclusion. Based on the assessment of original audiograms, patien…
How to optimize HCV therapy in genotype 1 patients: predictors of response.
2013
The advent of triple therapy (TT) with first-generation protease inhibitors boceprevir (BOC) and telaprevir (TVR) in addition to pegylated interferon and ribavirin (PEG-IFN/RBV) has resulted in a significant improvement in the sustained virological response (SVR) rate and potentially in life years gained compared to dual therapy (DT), when treating naive or treatment-experienced patients with genotype 1 (G1) chronic hepatitis C (CHC). This benefit is partly offset by the increased complexity of treatment, and the increased costs and risks of therapy, making it necessary to optimize the indications for TT. Naive patients with mild fibrosis and the IL28B CC polymorphism and/or with a rapid vi…
Pharmacogenomics of cetuximab in metastatic colorectal carcinoma
2014
Cetuximab is a chimeric monoclonal antibody that has revolutionized the treatment of metastatic colorectal cancer. Knowledge of the mechanisms that underlie its effectiveness, as well as the primary and secondary resistance mechanisms, have led to important developments in the understanding of cetuximab biology. In light of knowledge gained from recent trials, the efficacy of cetuximab has been clearly demonstrated to depend upon RAS mutational status, moreover cetuximab should only be used in a subset of patients who may benefit. In this article, we critically review clinical and pharmacogenetic issues of cetuximab, focusing on the cost–effectiveness involved with the use of the drug.
CYP2D6 genotype and adjuvant tamoxifen: meta-analysis of heterogeneous study populations.
2013
The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1); CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen…
Association Between CYP2D6 Polymorphisms and Outcomes Among Women With Early Stage Breast Cancer Treated With Tamoxifen
2009
Context The growth inhibitory effect of tamoxifen, which is used for the treatment of hormone receptor–positive breast cancer, is mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation of active metabolites is catalyzed by the polymorphic cytochrome P450 2D6 (CYP2D6) enzyme. Objective To determine whether CYP2D6 variation is associated with clinical outcomes in women receiving adjuvant tamoxifen. Design, Setting, and Patients Retrospective analysis of German and US cohorts of patients treated with adjuvant tamoxifen for early stage breast cancer. The 1325 patients had diagnoses between 1986 and 2005 of stage I through III breast cancer and were mainly postmenopausal (9…
Pharmacogenetics of treatments for pancreatic cancer
2019
Introduction: Despite clinical efforts, pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The scarcity of effective therapies can be reflected by the lack of reliable biomarkers to adapt anticancer drugs prescription to tumors’ and patients’ features. Areas covered: Pharmacogenetics should provide the way to select patients who may benefit from a specific therapy that best matches individual and tumor genetic profile, but it has not yet led to gains in outcome. This review describes PDAC pharmacogenetics findings, critically reappraising studies on polymorphisms and -omics profiles correlated to response to gemcitabine, FOLFIRINOX, and nab-paclitaxel combinations, as well as l…
MTHFR and VDR Polymorphisms Improve the Prognostic Value of MYCN Status on Overall Survival in Neuroblastoma Patients
2020
Single nucleotide polymorphisms (SNPs) in Pharmacogenetics can play an important role in the outcomes of the chemotherapy treatment in Neuroblastoma, helping doctors maximize efficacy and minimize toxicity. Employing AgenaBioscience MassArray, 96 SNPs were genotyped in 95 patients looking for associations of SNP with response to induction therapy (RIT) and grade 3&ndash
Pharmacogenetics implementation in the clinics: information and guidelines for germline variants.
2018
The aim of this work was to supply an overview of the germline Pharmacogenetics that can be already implemented in the oncology clinical practice. An explanation of the three pillars considered necessary for determining which genetic polymorphisms should be used has been provided. These are PharmGKB single nucleotide polymorphism (SNP)-Drug Clinical Annotations with levels of evidence 1 or 2; the genetic information provided in the drug labels by the drug regulatory main agencies (Food and Drug Administration and European Medicines Agency, mainly); and the guidelines elaborated by international expert consortia (mainly Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacoge…
Why should We Bother? Ethical and Social Issues in Individualized Medicine
2006
Individualized medicine, methodologically rooted in pharmacogenetics and pharmacogenomics, is now venturing into clinical application. Prescribing the right drug in the right dose to the right patient according to specific health needs and individual characteristics is a core mission of individualized medicine. The intrinsic values of this mission are so self-evident that--at first glance--the ethical and social issues raised by individualized medicine seem to be negligible. However, the translation of pharmacogenetics and pharmacogenomics into clinical routine not only requires the collection and evaluation of large amounts of individual genetic data, but also heralds the need for further …