Zusammenfassung
Das Lungenkarzinom gilt als Paradetumor für eine anhand prädiktiver Gewebediagnostik vorgenommene, stratifizierende Therapie und stellt daher zurzeit die Modellentität für die Entwicklung neuer diagnostischer und therapeutisch-individualisierter Behandlungsstrategien dar. Neue Entwicklungen sind hier insbesondere im Bereich prädiktiver Biomarker für konventionelle Chemotherapie, gezielte definierte genomische Alterationen adressierende Therapeutika, aber auch für neue immunmodulatorische Medikamente zu erwarten. Die sich ständig weiterentwickelnde Vielfalt an prädiktiven Biomarkern stellt hohe Anforderungen an die Implementierung effizienter Teststrategien und neuer technischer Methoden, um eine umfassende Analytik an dem im Lungenkarzinomkontext regelhaft spärlich zur Verfügung stehenden Gewebematerial zu ermöglichen. In der hier vorliegenden Arbeit werden sowohl inhaltliche als auch technische Aspekte dieser Entwicklung beleuchtet.
Abstract
Lung cancer is the prototypical tumor entity for the development of new diagnostic and individualized therapeutic strategies based on molecular patient stratification. Developments in this field specifically concentrate on predictive biomarkers for the response to conventional therapeutic agents, novel drugs targeting specific mutations and also new immunomodulatory drugs. The multitude of upcoming new predictive biomarkers requires the development and implementation of efficient test strategies and comprehensive technical methods, specifically when tissue restrictions inherent to lung cancer diagnostics are also taken into account. Novel procedures and technical aspects of these issues are discussed in this review.
Abbreviations
- ALK:
-
Anaplastische Lymphomkinase
- BRAF:
-
B-Raf-Protoonkogen
- CISH:
-
Chromogene In-situ-Hybridisierung
- CTLA4:
-
„Cytotoxic T-lymphocyte-associated protein 4“
- DDR2:
-
„Discoidin domain-containing receptor 2“
- DNA:
-
Desoxyribonukleinsäure
- EGFR:
-
Epidermaler Wachstumsfaktorrezeptor („epidermal growth factor receptor“)
- ERCC1:
-
„Excision repair cross-complementing rodent repair deficiency, complementation group 1“
- FFPE:
-
Formalin-fixiert and Paraffin-eingebettet
- FGFR:
-
Fibroblastenwachstumsfaktorrezeptor („fibroblast growth factor receptor“)
- FISH:
-
Fluoreszenz-in-situ-Hybridisierung
- KIT:
-
Protoonkogen-c-KIT
- KRAS:
-
„Kirsten rat sarcoma viral oncogene homolog“
- MALDI:
-
„Matrix-assisted laser desorption/ionization“
- MEK:
-
Mitogen-aktivierte Proteinkinase
- MPS:
-
Massive parallele Sequenzierung
- NGS:
-
„Next generation sequencing“
- NOS:
-
Nicht anderweitig spezifiziert („not otherwise specified“)
- NSCLC:
-
Nichtkleinzelliges Lungenkarzinom („non-small cell lung cancer“)
- PCR:
-
Polymerasekettenreaktion
- PD-1:
-
„Programmed cell death protein 1“
- PD-L1:
-
„Programmed death-ligand 1“
- PI3K:
-
Phosphoinositid-3-Kinase
- RET:
-
RET-Protoonkogen
- RNA:
-
Ribonukleinsäure
- ROS1:
-
ROS-Protoonkogen 1
- RRM1:
-
„Ribonucleotide reductase M1“
- SCLC:
-
Kleinzelliges Lungenkarzinom („small cell lung cancer“)
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Danksagung
Wir danken Dr. Rita Casadonte (Pathologie Trier) für die exzellente technische Unterstützung bei den massenspektrometrischen Untersuchungen.
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A. Warth, V. Endris, M. Kriegsmann, A. Stenzinger, R. Penzel, N. Pfarr, W. Weichert geben an, dass kein Interessenkonflikt besteht.
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C. Röcken, Kiel
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Warth, A., Endris, V., Kriegsmann, M. et al. Molekulardiagnostik des nichtkleinzelligen Lungenkarzinoms. Pathologe 36, 154–163 (2015). https://doi.org/10.1007/s00292-015-0004-4
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DOI: https://doi.org/10.1007/s00292-015-0004-4
Schlüsselwörter
- Lungenkarzinom
- Molekulare Diagnostik
- Sequenzielles Testen
- Massives paralleles Sequenzieren
- Immunmodulatorische Medikamente