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Personalisierte Onkologie

Personalized oncology

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Zusammenfassung

Klinisches Problem

Innovative „Next-generation-sequencing“(NGS)-Technologien und umfangreiche genomische Untersuchungen großer Patientenkohorten haben zu vielversprechenden personalisierten Therapiestrategien auf der Basis molekularer Charakteristika individueller Tumorerkrankungen geführt.

Therapeutische Standardverfahren

Zielgerichtete Medikamente wie Tyrosinkinaseinhibitoren, Antikörper oder moderne Immuntherapien sind als Mono- oder Kombinationstherapien zur Behandlung zahlreicher hämatologischer und onkologischer Erkrankungen etabliert.

Neue Therapieverfahren

Die Vielzahl moderner zielgerichteter Therapeutika, die an verschiedensten Komponenten intrazellulärer Signalkaskaden und onkogen wirksamen Mechanismen ansetzen, und die technische Möglichkeit NGS-basierter molekularer Diagnostik machen eine auf genomischen Alterationen basierende, entitätenübergreifende Therapieauswahl und molekulare Stratifizierung innerhalb klinischer Studien möglich.

Diagnostik

Umfangreichere genetische Untersuchungen wie Panelsequenzierungen oder Ganzexom‑, Ganzgenom- und Transkriptomsequenzierungen werden in unterschiedlichem Ausmaß und insbesondere an akademischen Zentren durchgeführt.

Leistungsfähigkeit

Prinzipiell ist eine umfangreiche Charakterisierung, die neben DNA- und RNA-Sequenzierung auch epigenetische, metabolomische und proteomische Veränderungen berücksichtigt, wünschenswert. Eine flächendeckende klinische Anwendung integrativer, multidimensionaler genetischer Befunde ist derzeit allerdings noch nicht möglich.

Bewertung

Es bleibt abzuwarten, inwieweit sich eine umfangreiche molekulare Diagnostik in eine signifikante Prognoseverbesserung übersetzen lässt und als diagnostisches Werkzeug breitere Anwendung finden kann.

Empfehlung für die Praxis

Die Auswahl der im Einzelfall sinnvollsten molekularen Diagnostik sollte u. a. von den gegebenen Möglichkeiten und der klinischen Situation abhängig gemacht werden.

Abstract

Clinical issue

Innovative next generation sequencing (NGS) technologies and comprehensive sequencing investigations in large patient cohorts have paved the way for very promising personalized treatment strategies based on the molecular characteristics of individual tumors.

Standard treatment

Targeted therapies, such as tyrosine kinase inhibitors, antibodies and modern immunotherapeutic approaches are well established as monotherapy and combination therapy for many hematological and oncological malignancies.

Treatment innovations

A plethora of innovative therapies targeting various components of intracellular signaling cascades and effective mechanisms against oncogenes as well as the availability of NGS technologies enable personalized cancer treatment based on the molecular profiles of individual tumors and genetic stratification, within clinical trials.

Diagnostic work-up

Comprehensive genetic approaches including cancer gene panel sequencing, whole exome, whole genome and transcriptome sequencing are carried out to a varying extent and particularly in the academic setting.

Performance

Principally, a comprehensive characterization of tumors in addition to DNA and RNA sequencing that also incorporates epigenetic, metabolomic, and proteomic alterations would be desirable. A comprehensive clinical implementation of integrative, multidimensional genetic typing is, however, currently not possible.

Achievements

It remains to be demonstrated whether these approaches will translate into significantly better outcomes for patients and whether they can be increasingly implemented in the routine diagnostic work-up.

Practical recommendations

The selection of diagnostic tools in individual cases and the extent of genomic analyses in the clinical context, need to take the availability of methods as well as the present clinical situation into account.

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Authors and Affiliations

  1. Abteilung für Translationale Onkologie, Nationales Centrum für Tumorerkrankungen Heidelberg, Im Neuenheimer Feld 460, 69120, Heidelberg, Deutschland

    C. Heining, P. Horak, S. Gröschel, H. Glimm &  S. Fröhling

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  1. C. Heining
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  2. P. Horak
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  3. S. Gröschel
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  4. H. Glimm
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Correspondence to S. Fröhling.

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Interessenkonflikt

C. Heining, P. Horak, S. Gröschel, H. Glimm und S. Fröhling geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

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Heining, C., Horak, P., Gröschel, S. et al. Personalisierte Onkologie. Radiologe 57, 804–811 (2017). https://doi.org/10.1007/s00117-017-0297-9

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