Article
Pharmacology & Pharmacy
Paula Soria-Chacartegui, Gonzalo Villapalos-Garcia, Luis A. Lopez-Fernandez, Marcos Navares-Gomez, Gina Mejia-Abril, Francisco Abad-Santos, Pablo Zubiaur
Summary: DPYD gene polymorphism can help predict toxicity in cancer patients treated with fluoropyrimidines, but its current predictive capacity is limited due to unknown mutations affecting enzyme function. Variant rs367619008, rs200643089, and rs76387818 were found to increase the percentage of explained toxicities, while further studies are needed to confirm the clinical relevance of variant rs944174134.
Article
Oncology
Daniel L. L. Hertz
Summary: This article calls for clinicians and clinical guidelines committees in the United States to re-evaluate the clinical utility of pretreatment DPYD testing. There is no direct evidence of efficacy reduction, and the available indirect evidence suggests that DPYD-guided FP dosing is well calibrated and minimizes the risk of reducing treatment efficacy.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Pharmacology & Pharmacy
Ursina B. M. Begre, Markus Jorger, Stefan Aebi, Ursula Amstutz, Carlo R. Largiader
Summary: Despite policies introduced for pre-treatment testing of DPYD gene risk variants in Switzerland, there was no significant increase in testing requests until the release of recommendations by the European Medicines Agency in April 2020, leading to a 14-fold increase in DPYD testing.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Claire Palles, Susan Fotheringham, Laura Chegwidden, Marie Lucas, Rachel Kerr, Guy Mozolowski, Dan Rosmarin, Jenny C. Taylor, Ian Tomlinson, David Kerr
Summary: 5-Fluorouracil (5-FU) is a chemotherapy drug that can cause severe toxicity in some patients, due to variations in a protein called dihydropyrimidine dehydrogenase (DPD) impacting the clearance of the drug. This study aims to assess the frequency of DPD deficiency variants in patients and their predictive value for 5-FU induced toxicity, providing important insights for identifying high-risk patients and optimizing treatment strategies. Genotyping specific alleles can significantly improve the accuracy of predicting adverse events associated with 5-FU chemotherapy.
Review
Oncology
Bhavina B. Sharma, Karan Rai, Heather Blunt, Wenyan Zhao, Tor D. Tosteson, Gabriel A. Brooks
Summary: This study systematically evaluated the risk of treatment-related death associated with DPYD gene variants during fluoropyrimidine chemotherapy, and found that patients with pathogenic DPYD gene variants have a significantly increased risk of treatment-related death.
Article
Pharmacology & Pharmacy
Nada Bozina, Ivan Bilic, Lana Ganoci, Livija Simicevic, Stjepko Plestina, Lucija Lesnjakovic, Vladimir Trkulja
Summary: Pathologists found that DPYD c.496A>G and possibly c.2194G>A variants may need to be considered for inclusion in the DPYD genotyping panel.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Eiji Hishinuma, Yoko Narita, Kai Obuchi, Akiko Ueda, Sakae Saito, Shu Tadaka, Kengo Kinoshita, Masamitsu Maekawa, Nariyasu Mano, Noriyasu Hirasawa, Masahiro Hiratsuka
Summary: In this study, an in vitro analysis was conducted on 41 DPD allelic variants to investigate changes in enzymatic activity, with 7 variants showing significantly decreased activity and 2 variants displaying no enzymatic activity. Our findings suggest that DPD dimerization is essential for enzymatic activity and these variants may contribute to the observed inter-individual variability in the pharmacokinetics and pharmacodynamics of 5-FU. Additionally, rare DPYD variants, although at low frequencies, could serve as important pharmacogenomic markers associated with severe 5-FU toxicity in the Japanese population.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Lucija Lesnjakovic, Lana Ganoci, Ivan Bilic, Livija Simicevic, Iva Mucalo, Stjepko Plestina, Nada Bozina
Summary: FPs are widely used antineoplastic drugs for solid tumors treatment, but they can cause severe toxicity, especially in patients with reduced DPD activity. European agencies recommend pre-treatment DPD deficiency screening, but American ones do not. Current guidelines recommend testing four DPD gene risk variants, but new evidence on additional common DPYD polymorphisms and rare DPYD variants may help address the missing heritability of DPD deficiency and FP-related toxicity.
Article
Pharmacology & Pharmacy
Seid Hamzic, Dominic Schaerer, Steven M. Offer, Didier Meulendijks, Christos Nakas, Robert B. Diasio, Stefano Fontana, Marc Wehrli, Stefan Schuerch, Ursula Amstutz, Carlo R. Largiader
Summary: This study identified specific genetic variants associated with decreased DPD activity and higher risk of severe toxicity to 5-FU chemotherapy.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Daniel L. Hertz, D. Max Smith, Stuart A. Scott, Jai N. Patel, J. Kevin Hicks
Summary: FP chemotherapy has severe toxicities for patients with DPYD gene variants. DPYD testing is standard in Europe but not recommended in the US. The FDA updated the capecitabine package insert to inform patients about the toxicity risk and test availability, but without specific recommendations for testing or dose adjustment. It is important for the FDA to follow European recommendations and promote DPYD testing and genotype-based dose adjustment.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Oncology
Mirjam de With, Gemma Brufau, Laila A. van den Berg, Femke M. de Man, Marija Trajkovic, Martine F. Thijs, Rob Castel, Henricus J. Vermeer, Samira el Bouazzaoui, Amber van Hemel, Maja Matic, Ron H. J. Mathijssen, Sander Bins, Ron H. N. van Schaik
Summary: The study confirms that 46% of patients carrying the DPYD*7 variant allele develop severe treatment-related adverse events, even with initial dose reductions. This highlights the need for prospective studies to investigate the required fluoropyrimidine dose for DPYD*7 carriers.
JCO PRECISION ONCOLOGY
(2022)
Review
Oncology
Robert B. Diasio, Steven M. Offer
Summary: This review discusses methods for identifying individuals at high risk for severe side effects in 5-FU therapy.
Review
Health Care Sciences & Services
Woorim Kim, Young-Ah Cho, Dong-Chul Kim, Kyung-Eun Lee
Summary: This study aimed to evaluate the risk of fluoropyrimidine-associated toxicity in patients with DPYD rs1801160 polymorphism. The systematic literature review and meta-analysis revealed an association between rs1801160 polymorphism and fluoropyrimidine-associated toxicity.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Ottavia De Luca, Gerardo Salerno, Donatella De Bernardini, Maria Simona Torre, Maurizio Simmaco, Luana Lionetto, Giovanna Gentile, Marina Borro
Summary: NGS exon sequencing can explain approximately 42.5% of DPD deficiencies, significantly improving the prediction of DPD deficiencies, but more genotype-phenotype association data is needed for clinical use.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
P. Garcia-Alfonso, M. Saiz-Rodriguez, R. Mondejar, J. Salazar, D. Paez, A. M. Borobia, M. J. Safont, I Garcia-Garcia, R. Colomer, X. Garcia-Gonzalez, M. J. Herrero, L. A. Lopez-Fernandez, F. Abad-Santos
Summary: Genotyping DPYD gene polymorphisms before administering fluoropyrimidines can help classify individuals as normal, intermediate, or poor metabolizers, allowing for personalized treatment strategies to avoid toxicities. The consensus aims to provide clear recommendations for implementing genotype and/or phenotype testing for DPD deficiency in cancer patients receiving fluoropyrimidines.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2022)
Article
Allergy
Michael P. Horn, Hulda R. Jonsdottir, Daniel Brigger, Lauro Damonti, Franziska Suter-Riniker, Olga Endrich, Tanja K. Froehlich, Martin Fiedler, Carlo R. Largiader, Jonas Marschall, Benjamin Weber, Alexander Eggel, Michael Nagler
Summary: This study evaluated the diagnostic accuracy of various serological testing strategies for COVID-19 in real-life clinical settings. The results showed that different testing methods and antibody subtypes had varying levels of sensitivity and specificity. These findings are important for estimating the infection burden in specific populations and predicting the likelihood of immune protection.
Article
Multidisciplinary Sciences
Antonio Rodriguez-Calero, John Gallon, Dilara Akhoundova, Sina Maletti, Alison Ferguson, Joanna Cyrta, Ursula Amstutz, Andrea Garofoli, Viola Paradiso, Scott A. Tomlins, Ekkehard Hewer, Vera Genitsch, Achim Fleischmann, Erik Vassella, Elisabeth J. Rushing, Rainer Grobholz, Ingeborg Fischer, Wolfram Jochum, Gieri Cathomas, Adeboye O. Osunkoya, Lukas Bubendorf, Holger Moch, George Thalmann, Charlotte K. Y. Ng, Silke Gillessen, Salvatore Piscuoglio, Mark A. Rubin
Summary: Improved therapies for prostate cancer have led to an increase in brain metastases. By studying the genetic alterations in brain metastases from prostate cancer patients, researchers have found higher mutational burden and enrichment of homologous recombination deficiency mutational signature. Some patients may benefit from PARP inhibitors.
NATURE COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Ursina B. M. Begre, Markus Jorger, Stefan Aebi, Ursula Amstutz, Carlo R. Largiader
Summary: Despite policies introduced for pre-treatment testing of DPYD gene risk variants in Switzerland, there was no significant increase in testing requests until the release of recommendations by the European Medicines Agency in April 2020, leading to a 14-fold increase in DPYD testing.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Tamana Meihandoest, Jan-Dirk Studt, Adriana Mendez, Lorenzo Alberio, Pierre Fontana, Walter A. Wuillemin, Adrian Schmidt, Lukas Graf, Bernhard Gerber, Ursula Amstutz, Cedric Bovet, Thomas C. Sauter, Lars M. Asmis, Michael Nagler
Summary: In this study, a heparin-calibrated anti-Xa assay was found to accurately measure the drug concentrations of rivaroxaban, apixaban, and edoxaban, and correctly predict clinically relevant levels.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Genetics & Heredity
Nicholas Kueng, Severine Arcioni, Fanny Sandberg, Christian Kuhn, Vanessa Banz, Carlo R. Largiader, Daniel Sidler, Ursula Amstutz
Summary: Liquid biopsy using quantification of donor-derived cell-free DNA (dd-cfDNA) in plasma has become a novel approach for allograft monitoring in solid organ transplant recipients. This study compared different dd-cfDNA quantification methods and found that the presented high-throughput sequencing method showed strong correlation with existing methods. Absolute levels of dd-cfDNA in urine may be required for allograft surveillance in stable kidney recipients due to extensive variability of relative amounts.
FRONTIERS IN GENETICS
(2023)
Article
Oncology
John Gallon, Antonio Rodriguez-Calero, Andrej Benjak, Dilara Akhoundova, Sina Maletti, Ursula Amstutz, Ekkehard Hewer, Vera Genitsch, Achim Fleischmann, Elisabeth J. Rushing, Rainer Grobholz, Ingeborg Fischer, Wolfram Jochum, Gieri Cathomas, Adeboye O. Osunkoya, Lukas Bubendorf, Holger Moch, George Thalmann, Felix Y. Feng, Silke Gillessen, Charlotte K. Y. Ng, Mark A. Rubin, Salvatore Piscuoglio
Summary: Metastases from primary prostate cancers to rare locations, such as the brain, are becoming more common due to longer life expectancy. Epigenetic dysregulation and distinct DNA methylation profiles are associated with primary prostate cancer and prostate cancer brain metastases (PCBM). This study analyzed the DNA methylation landscapes of PCBM, identified associations with mutational background and PRC2 complex activity, and discovered specific epigenetic alterations potentially involved in PCBM formation.
Article
Oncology
Cedric Gillich, Dilara Akhoundova, Michael Hayoz, Yolanda Aebi, Carlo R. Largiader, Katja Seipel, Michael Daskalakis, Ulrike Bacher, Thomas Pabst
Summary: Upfront treatment consolidation with TreoMel HDCT and ASCT has promising efficacy and safety in MM patients, achieving a complete response rate of 84% and an OS rate of 83%. Treosulfan pharmacokinetics showed no significant correlation with MM responses, but higher exposure and peak value in female patients were associated with longer hospitalizations.
Article
Oncology
M. de With, A. Sadlon, E. Cecchin, V. Haufroid, F. Thomas, M. Joerger, R. H. N. van Schaik, R. H. J. Mathijssen, C. R. Largiader
Summary: After the release of the EMA recommendations, there was an increase in both genotype and phenotype testing in Europe. Some countries also implemented new local guidelines. Although challenges such as lack of reimbursement and awareness among medical oncologists still existed, the percentage of specialists citing these hurdles decreased after the EMA recommendations.
Article
Infectious Diseases
Peter J. Neyer, Berenger Kabore, Christos T. Nakas, Britta Hartmann, Annelies Post, Salou Diallo, Halidou Tinto, Angelika Hammerer-Lercher, Carlo R. Largiader, Andre J. van der Ven, Andreas R. Huber
Summary: This study investigated the associations between iron homeostasis, inflammation, nutrition, and haemoglobin mutations with asymptomatic malaria infection. The results showed that malnutrition was strongly associated with asymptomatic parasitaemia, and the presence of haemoglobin S mutation could attenuate the infection.
Article
Medicine, General & Internal
Nicholas Kueng, Daniel Sidler, Vanessa Banz, Carlo R. R. Largiader, Charlotte K. Y. Ng, Ursula Amstutz
Summary: This study evaluated the technical biases of single- and double-stranded library preparation methods when applied on cfDNA from plasma and urine, and assessed the proportions of tissue of origin using two deconvolution methods. The results showed that sequencing cfDNA from urine using the double-stranded method resulted in methylation bias and lower global methylation, which were not observed with the single-stranded approach. The deconvolution methods also yielded different results in terms of determining tissue of origin proportions.
Meeting Abstract
Oncology
Huixing Huang, Dominic Schaerer, Remington Schmidt, Ting Zhang, Tanja K. Froehlich, Kelly Bouchonville, Robert B. Diasio, Ursula Amstutz, Carlo Largiader, Steven M. Offer
Meeting Abstract
Clinical Neurology
E. S. Wenz, J. -C. Prost, G. M. Mader, I. Filchenko, J. D. Warncke, M. H. Schmidt, C. R. Largiader, C. L. A. Bassetti
JOURNAL OF SLEEP RESEARCH
(2022)
Meeting Abstract
Clinical Neurology
E. Wenz, J. Prost, I. Filchenko, J. Warncke, M. Schmidt, C. Largiader, C. Bassetti
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Meeting Abstract
Oncology
Ting Zhang, Alisa Ambrodji, Huixing Huang, Kelly Bouchonville, Amy Etheridge, Remington Schmidt, Jose Cardiel Nunez, Zoey Temesgen, Federico Innocenti, Robert Diasio, Carlo Largiader, Steven M. Offer