Aktuelle Entwicklung der molekular zielgerichteten Therapie von Kopf-Hals-Karzinomen

Zusammenfassung

Rezidivsituation und Fernmetastasierung stellen bei Plattenepithelkarzinomen des Kopf-Hals-Bereichs (HNSCC) eine große therapeutische Herausforderung dar. Es besteht für die betroffenen Patienten eine hohe Morbidität sowie meist eine unbefriedigende, mediane Gesamtüberlebensrate selbst unter intensiven Kombinationschemotherapien. Die Einführung des Epidermal Growth Factor Receptor (EGFR)-Antikörpers Cetuximab 2008 stellte in Verbindung mit einer platinhaltigen Chemotherapie eine erste Verbesserung in Bezug auf das Gesamtüberleben seit Jahrzehnten dar. Da aber eine Monotherapie mit Cetuximab bei besserer Verträglichkeit eine deutlich geringere Effektivität als eine Kombination mit platinhaltiger Chemotherapie aufweist, besteht großer Bedarf, neue Ziele für zielgerichtete Therapien zu identifizieren und mögliche Kombinationen zu evaluieren. Neue Zielstrukturen umfassen EGFR und seine nachgeschalteten Rezeptor- Tyrosinkinasen, sowie Inhibitoren des VEGF- und des PI3K/AKT/ mTOR-Signalweges. Ferner liegt aktuell großes Potenzial in einer Immuntherapie mittels Checkpoint-Blockade. Aufgrund der nur eingeschränkten Effektivität einer zielgerichteten Monotherapie sind gegenwärtig mögliche Kombinationstherapien und deren Toxizitäten sowie der Zeitpunkt des Therapiebeginns von großem klinischem Interesse.

Abstract

Recurrent squamous cell carcinomas of the head and neck (HNSCC) is a challenging disease due to morbidity and limited median overall survival rates even after aggressive chemotherapeutic regimen. The clinical establishment of the epidermal growth factor receptor (EGFR) antibody Cetuximab in 2008 brought the first significant survival benefit in palliative chemotherapy of HNSCC for decades. With regard to rather high toxicity of palliative chemotherapy and low remission rates after Cetuximab monotherapy, there is an urgent need for new targeted therapies.

New targeted therapeutics include antagonists of EGFR and its downstream kinases, as well as inhibitors of VEGF- and PI3K/AKTmTOR signaling pathways. Furthermore, novel immunological checkpoint inhibition provides new hopeful perspectives.

Due to limited remission rates of monotherapies using antibodies or tyrosine kinase inhibitors the evaluation of less toxic combination therapies is of great current clinical interest.

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