Molekulare Tumordiagnostik als Triebfeder der Präzisionsonkologie

Die Weiterentwicklung molekularpathologischer Diagnostik ist relevant für jeden onkologischen Patienten, für prospektive klinische Studien und für die Generierung von Realwelt-Daten zur Medikamentenentwicklung. Die Verbesserung einer skalierbaren Molekulardiagnostik und die Entwicklung adaptiver Diagnostikstrategien ist notwendig, um die enorme Plastizität einer Krebserkrankung im zeitlichen Verlauf abbilden zu können.

Abstract

Molecular pathological diagnostics plays a central role in personalized oncology and requires multidisciplinary teamwork. It is just as relevant for the individual patient who is being treated with an approved therapy method or an individual treatment attempt as it is for prospective clinical studies that require the identification of specific therapeutic target structures or complex biomarkers for study inclusion. It is also of crucial importance for the generation of real-world data, which is becoming increasingly important for drug development. Future developments will be significantly shaped by improvements in scalable molecular diagnostics, in which increasingly complex and multi-layered data sets must be quickly converted into clinically useful information. One focus will be on the development of adaptive diagnostic strategies in order to be able to depict the enormous plasticity of a cancer disease over time.

Kernaussagen

• Die umfassenderen genomischen Analysen der Bioinformatik erhöhen die Komplexität und somit die Anforderungen an die bioinformatische Expertise.

• Die erfolgreiche Nutzung molekularer Diagnostik kann nur mit einem multidisziplinären Team bewerkstelligt werden.

• Mutationssignaturen bilden ein Mutationsporträt der Tumorentwicklung und können Aufschluss darüber geben, welche Mutationsprozesse im Laufe der Zeit wirkten.

• Um die Integration von Mutationssignaturen in die klinische Entscheidungsfindung weiter zu erhöhen, ist es wichtig, dass alternative Sequenzierungsansätze entwickelt und genutzt werden.

• Die arraybasierte Methylierungsanalyse wird aufgrund ihrer standardisierten Technologie sowie ihrer technischen Einfachheit und Robustheit bei der Verwendung von DNA aus formalinfixierten Tumorproben am häufigsten verwendet.

• RNA-Sequenzierung hat sich als wertvolles Werkzeug für den Nachweis von Genfusionen in der prädiktiven Tumordiagnostik erwiesen.

• Ein zukünftiges klinisch-diagnostisches Anwendungsfeld der umfassenden RNA-Sequenzierung kann die unterstützende diagnostische Einordnung von Karzinomen unbekannter Primärerkrankung (CUP) darstellen.

• Die Integration von umfassenden Proteomanalysen in der Molekularpathologie ist noch nicht weit verbreitet, bietet aber ein großes diagnostisches Potenzial.

• Die Generalisierbarkeit maschineller Lernmodelle und das Blackbox-Design von KI-Ansätzen sind herausfordernde Eigenschaften dieser neuen Technik und stellen mögliche Einschränkungen dar.

Schlüsselwörter

molekulare Tumordiagnostik, - Bioinformatik - Mutationssignaturen - Methylierungsarrays - künstliche Intelligenz

Keywords

molecular tumor diagnostics - bioinformatics - mutation signatures - methylation arrays - artificial intelligence

Publication History

Article published online:
01 September 2023

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