Consolidated BRCA1/2 Variant Interpretation by MH BRCA Correlates with Predicted PARP Inhibitor Efficacy Association by MH Guide

Publikation

Consolidated BRCA1/2 Variant Interpretation by MH BRCA Correlates with Predicted PARP Inhibitor Efficacy Association by MH Guide

BRCA1/2-Varianten sind prognostische Biomarker für das erbliche Brust- und / oder Eierstockkrebs-Syndrom (HBOC) und prädiktive Biomarker für die PARP-Hemmung. In dieser Studie haben wir die Klassifizierung von BRCA1 / 2-Varianten von Patienten mit HBOC-bedingtem Krebs mithilfe von MH BRCA bewertet, ein/er neuartigen Computertechnologie, die die ACMG-Richtlinien mit von Experten kuratierten Variantenanmerkungen kombiniert.

 

Mehr dazu (auf Englisch): https://www.mdpi.com/1422-0067/21/11/3895/htm

Präzisionsonkologie – Die Suche nach Evidenz.

Publikation

Präzisionsonkologie – Die Suche nach Evidenz.

Die molekulare Charakterisierung von Tumoren bei Patienten bietet einen rationalen und vielversprechenden Ansatz, um Onkologen bei der Entscheidungsfindung bei der Behandlung zu unterstützen. Ungeachtet dessen steckt die genomische Medizin noch in den Kinderschuhen. Innovatoren und Early Adopters tragen weiterhin einen erheblichen Teil des klinischen und finanziellen Risikos.

https://www.ncbi.nlm.nih.gov/pubmed/31492009

Disease Interception – Onkologie & Genetik: Evidenzbasierte Interception für Prävention und Therapie

Publikation

Disease Interception – Onkologie & Genetik: Evidenzbasierte Interception für Prävention und Therapie

Krankheiten erkennen und aufhalten, bevor sie ausbrechen, ist eine faszinierende Vorstellung. Disease Interception hat genau dies zum Ziel. Das Konzept sieht vor, Betroffene deutlich früher zu diagnostizieren und zu therapieren als heute – vor dem Auftreten klinischer Symptome – und den Krankheitsprozess noch im präklinischen Stadium zu unterbrechen. Disease Interception würde einen Paradigmenwechsel für Betroffene, ihre Angehörigen, Ärzte und das Gesundheitssystem insgesamt bedeuten. Damit einher gehen Fragen, die weit über die Medizin hinausreichen, darunter gesellschaftliche, regulatorische, rechtliche und ethische Fragen. Um sie zu beantworten, bedarf es eines Diskurses aller Akteure. Die Publikation „Disease Interception“, unterstützt von Janssen Deutschland, leistet dazu einen Beitrag.

Die Herausgeber, Prof. Dr. med. Frank Jessen und Dr. med. Christoph Bug, haben namhafte Experten aus Medizin, Forschung, Gesundheitswirtschaft und Gesellschaft eingeladen, das Konzept der Disease Interception zu bewerten: D. Berron | F. von Bohlen und Halbach | C. Bug | M. Danner | E. Düzel | M. Hennrich | W. Hoffmann | F. Jessen | F. Knieps | P. Langkafel | J.-M. Löhr | D. Matusiewicz | S. Maul | M.-S. Raab | H. Rebscher | R. Roski | D. Rujescu | C. Stallberg | A. Ullmann | J. Wasem | J. Werner | J. Wiltfang | E. Winkler | I. Zwingmann

Disease Interception ist definiert durch Biomarker, welche die Entdeckung einer Erkrankung ermöglichen, bevor der Patient Symptome zeigt, um ihn sodann noch vor Ausbruch der eigentlichen Krankheit kurativ zu behandeln. Dieses hehre Ziel ist heute in der Onkologie nur ansatzweise und schon gar nicht durchgängig verwirklicht.

Zum Beitrag von Prof. Matthias Löhr, Karolinska Institut, und Dr. Friedrich von Bohlen, CEO Molecular Health:
https://www.monitor-versorgungsforschung.de/DI/DI-PDFs/DI-Beitrag_vBohlenundHalbach_Loehr

Adverse Event Circumstances and the Case of Drug Interactions.

Publikation

Adverse Event Circumstances and the Case of Drug Interactions.

Adverse events are a common and for the most part unavoidable consequence of therapeutic intervention. Nevertheless, available tomes of such data now provide us with an invaluable opportunity to study the relationship between human phenotype and drug-induced protein perturbations within a patient system. Deciphering the molecular basis of such adverse responses is not only paramount to the development of safer drugs but also presents a unique opportunity to dissect disease systems in search of novel response biomarkers, drug targets, and efficacious combination therapies. Inspired by the potential applications of this approach, we first examined adverse event circumstances reported in FAERS and then performed a molecular level interrogation of cancer patient adverse events to investigate the prevalence of drug-drug interactions in the context of patient responses. We discuss avoidable and/or preventable cases and how molecular analytics can help optimize therapeutic use of co-medications. While up to one out of three adverse events in this dataset might be explicable by iatrogenic, patient, and product/device related factors, almost half of the patients in FAERS received multiple drugs and one in four may have experienced effects attributable to drug interactions.

 

Healthcare Basel. 2019 Mar 19;7(1); Soldatos, Jackson. doi: 10.3390/healthcare7010045.

In Silico Profiling of Clinical Phenotypes for Human Targets Using Adverse Event Data.

Publikation

In Silico Profiling of Clinical Phenotypes for Human Targets Using Adverse Event Data.

We present a novel approach for the molecular transformation and analysis of patient clinical phenotypes. Building on the fact that drugs perturb the function of targets/genes, we integrated data from 8.2 million clinical reports detailing drug-induced side effects with the molecular world of drug-target information. Using this dataset, we extracted 1.8 million associations of clinical phenotypes to 770 human drug-targets. This collection is perhaps the largest phenotypic profiling reference of human targets to-date, and unique in that it enables rapid development of testable molecular hypotheses directly from human-specific information. We also present validation results demonstrating analytical utilities of the approach, including drug safety prediction, and the design of novel combination therapies. Challenging the long-standing notion that molecular perturbation studies cannot be performed in humans, our data allows researchers to capitalize on the vast tomes of clinical information available throughout the healthcare system.

 

Soldatos, Taglang, Jackson; High Throughput. 2018 Nov 23;7(4). doi: 10.3390/ht7040037.

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data.

Publikation

Retrospective Side Effect Profiling of the Metastatic Melanoma Combination Therapy Ipilimumab-Nivolumab Using Adverse Event Data.

Recent studies suggest that combining nivolumab with ipilimumab is a more effective treatment for melanoma patients, compared to using ipilimumab or nivolumab alone. However, treatment with these immunotherapeutic agents is frequently associated with increased risk of toxicity, and (auto-) immune-related adverse events. The precise pathophysiologic mechanisms of these events are not yet clear, and evidence from clinical trials and translational studies remains limited. Our retrospective analysis of ~7700 metastatic melanoma patients treated with ipilimumab and/or nivolumab from the FDA Adverse Event Reporting System (FAERS) demonstrates that the identified immune-related reactions are specific to ipilimumab and/or nivolumab, and that when the two agents are administered together, their safety profile combines reactions from each drug alone. While more prospective studies are needed to characterize the safety of ipilimumab and nivolumab, the present work constitutes perhaps the first effort to examine the safety of these drugs and their combination based on computational evidence from real world post marketing data.

Diagnostics (Basel). 2018 Oct 31;8(4); Soldatos TG. doi: 10.3390/diagnostics8040076.

Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer.

Publikation

Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer.

Stecker, Huelsewig, Brock, Jackson. 2017; Mol Oncol. 2017 Oct;11(10):1413-1429.