Strahlentherapie und molekular zielgerichtete Therapie – alles gezielt?

The targeted inhibition of DNA repair mechanisms and other intracellular signaling cascades is considered a promising tool for the local enhancement of radiotherapy. The epidermal growth factor receptor (EGFR) antagonist cetuximab is so far the only targeted agent approved for use in combination with radiotherapy. A large number of targeted combination therapies are currently undergoing clinical trials.

Inhibitors of various DNA repair mechanisms (ATM, ATR, DNA-PK, WEE1, PARP) as well as antagonists of inhibitors of apoptosis proteins (IAPs) are being tested in combination with radiotherapy in phase I and II trials. Phase III trials are, among others, currently being conducted in the chemoradiotherapy of head and neck squamous cell carcinoma (HNSCC) with the IAP antagonist xevinapant, which demonstrated a clear survival advantage with a low toxicity profile in a phase II trial.

There is a wealth of promising preclinical data on the combination of targeted drugs and radiotherapy with regard to radiation sensitization of tumors. However, the transfer of preclinically effective concepts to the clinical setting is proving difficult. Most advanced is the phase III trial on xevinapant in chemoradiotherapy of HNSCC, with results expected in 2024. Strategies for the effective use of targeted therapy with radiotherapy could include research into biomarkers and the development of innovative study concepts.