Zusammenfassung
Das Plattenepithelkarzinom des Penis („squamous cell carcinoma of the penis“, SCCP) ist in den westlichen Industrienationen zwar selten, weist jedoch in den fortgeschrittenen Tumorstadien einen aggressiven Erkrankungsverlauf auf mit einer dann hohen rezidiv- und karzinombedingten Mortalitätsrate. Aktuell sind keine molekularen Biomarker in der klinischen Routine bei SCCP-Patienten etabliert. Der diesbezügliche Bedarf ist jedoch immens, da geeignete Biomarker in der Prognosedeterminierung, der Festlegung von Art und Ausmaß der Primärtherapie, der Indikationsstellung zur inguinalen Lymphadenektomie bzw. adjuvanten Therapie und auch als Targets für eine gerichtete systemische Therapie sinnvoll einzusetzen wären. Das SCCP entwickelt sich aus der Progression einer Precursor-Läsion und hierbei ist ein HPV-abhängiger (HPV: humane Papillomaviren) von einem HPV-unabhängigen Pathway zu unterscheiden. In der Entschlüsselung der genetischen und epigenetischen Signaturen der distinkten molekularen Pathways liegt das Potential für eine jeweilige erfolgversprechende gerichtete Therapie. Hierzu ist eine Zunahme der translationalen Forschung in großen multiinstitutionalen Kollaborationen zu fordern, um nachfolgend auf dieser Basis effektive gerichtete (personalisierte) Therapiestrategien entwickeln zu können. Der hier vorliegende Reviewartikel soll konzis den gegenwärtigen Forschungsstand zu den molekularen Veränderungen des SCCP unter separater Berücksichtigung der zur Prognose untersuchten molekularen Marker einerseits und der als erfolgversprechende Therapietargets erscheinenden Biomarker andererseits abbilden. Zudem werden kurz die bisherigen Forschungsaktivitäten der eigenen Arbeitsgruppe zu diesem Thema dargestellt.
Abstract
Squamous cell carcinoma of the penis (SCCP) is a rare cancer type in Western industrialized nations; nevertheless, it shows an aggressive course of disease in advanced tumor stages with accordantly high recurrence and progression rates. While molecular biomarkers are not established in clinical routine for the management of SCCP patients yet, the accordant unmet need is enormous, as adequate biomarkers would be meaningful for prognostic determination, planning of modality and extent of primary therapy, indication for inguinal lymph node resection, adjuvant treatment, and as potential targets for specific systemic treatment. SCCP regularly develops from a precursor lesion. In this regard, human papillomavirus (HPV)-dependent and -independent pathways are differentiated. The potential for specific target therapy options is mainly based on the decoding of genetic and epigenetic signatures of distinct molecular pathways. In order to develop targeted and personalized treatment strategies based on molecular pathways, an increase in translational research in large multi-institutional collaborations must be promoted. This review article aims to summarize the current status of research concerning molecular changes related to SCCP under separate consideration of prognostic molecular markers, on the one hand, and biomarkers considered potential therapeutic targets, on the other hand. In addition, previous research activities of our own working group on this topic are briefly described.
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Danksagung
Die Autoren bedanken sich ganz herzlich bei Herrn Prof. Dr. med. Stefan Koch, Direktor des Pathologischen Instituts im Helios-Klinikum Bad Saarow, für seine Anmerkungen zu der vorliegenden Arbeit und bei Herrn Dr. med. Sven Gunia, Oberarzt des Pathologischen Instituts im Vivantes-Humboldt-Klinikum Berlin, für die Anfertigung der aussagekräftigen Abbildungen.
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M. May, S.D. Brookman-May, T.H. Ecke und M. Burger geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.
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May, M., Brookman-May, S.D., Ecke, T.H. et al. Die molekulare Charakterisierung des Peniskarzinoms. Urologe 57, 398–407 (2018). https://doi.org/10.1007/s00120-018-0596-4
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DOI: https://doi.org/10.1007/s00120-018-0596-4