Molekulare Ansatzpunkte für systemische Therapien adenoidzystischer Karzinome im Kopf-Hals-Bereich

 

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Zusammenfassung

Das adenoidzystische Karzinom (ACC) ist ein neurotroper Speicheldrüsentumor mit einer hohen hämatogenen Metastasierungstendenz. Die Therapie der Wahl ist bei lokal begrenztem Wachstum die vollständige chirurgische Resektion und in Abhängigkeit vom Resektionsstatus eine adjuvante Strahlentherapie. Aufgrund der verhältnismäßig hohen Rezidivrate mit eingeschränkter lokaler Interventionsmöglichkeit und der im weiteren langfristigen Krankheitsverlauf häufig vorzufindenden hämatogenen Fernmetas­tasen, wird man als Therapeut zwangsläufig mit der Frage nach einer adäquaten systemischen Therapie konfrontiert. Die Ansprechraten des Tumors sind bei einer Vielzahl der eingesetzten Chemotherapeutika als gering zu bezeichnen, anhaltende Komplettremissionen oder gar Heilungen sind äußerst selten. Neben der klassischen Chemotherapie kommen Immuntherapeutika und „Targetsubstanzen“ mit z. T. günstigem Nebenwirkungsprofil zum Einsatz, wobei aufgrund der geringen Patientenzahlen in den zur Verfügung stehenden Studien eine definitive Aussage zur Effektivität kaum gemacht werden kann. Hieraus ergibt sich die Notwendigkeit zu multizentrischen Studienbemühungen, die im prospektiven Design klare Handlungsempfehlungen zur Systemtherapie des Tumors erlauben. Die vorliegende Arbeit gibt eine Übersicht zu den subzellulären und genetischen Charakteristika des ACC, die einen Angriffspunkt für systemische Therapiebemühungen darstellen und teilweise in klinischen Studien bereits Berücksichtigung gefunden haben.

Abstract

The adenoid cystic carcinoma (ACC) is a neurotropic salivary gland tumor with a high blood-borne metastasis tendency. The treatment of choice for localized disease consists of radical surgical resection and, depending on resection status, adjuvant radiotherapy. Due to the high recurrence rate with limited local therapeutic options and frequent occurrence of distant metastases, one is confronted inevitably with the search for an adequate systemic therapy. ACC shows little response to a variety of chemotherapeutic agents, partial or complete remissions are extremely rare. Beside classical chemotherapies, immunotherapeutics and targeted therapies with more favorable side effect profiles were tested in trials, but due to the small number of patients, a definitive statement on the effectiveness can be hardly made. This results in the need for prospective multicenter studies that allow clear recommendations for systemic therapy of the tumor. The present paper gives an overview of the sub-cellular and genetic characteristics of ACC, which represent possible targets for systemic therapies and have partly already been included in running clinical trials.

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