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Radioprotection of normal tissue cells

Strahlenschutz von Normalgewebszellen

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Abstract

Improvements of radiotherapy in combination with surgery and systemic therapy have resulted in increased survival rates of tumor patients. However, radiation-induced normal tissue toxicity is still dose limiting. Several strategies have been pursued with the goal to develop substances which may prevent or reduce damage to normal tissue. Drugs applied before radiotherapy are called radioprotectors; those given after radiotherapy to reduce long-term effects are radiomitigators. Despite more than 50 years of research, until now only two substances, amifostine and palifermin, have overcome all obstacles of clinical approval and are applied during radiotherapy of head and neck cancer or total body irradiation, respectively. However, better understanding of the cellular pathways involved in radiation response has allowed the development of several highly promising drugs functioning as scavengers of reactive oxygen species or targeting specific molecules involved in regulation of cell death pathways or cell cycle arrest. The present review describes the major targets for radioprotectors or radiomitigators currently tested in clinical trials.

Zusammenfassung

Verbesserungen in der Radiotherapie in Kombination mit Chirurgie und Chemotherapie führten zu erhöhten Überlebensraten von Tumorpatienten. Trotzdem sind Strahlenfolgen am Normalgewebe weiterhin dosislimitierend. Verschiedene Ansätze wurden verfolgt, um Substanzen zu entwickeln, die Normalgewebstoxizitäten verhindern oder verringern. Medikamente, die vor der Radiotherapie verabreicht werden, heißen Radioprotektoren, solche die danach gegeben werden, um langfristige Effekte zu reduzieren, Radiomitigatoren. Trotz mehr als 50 Jahre Forschung überwanden nur zwei Substanzen, Amifostin und Palifermin, alle Hürden der klinischen Prüfung und sind für die Anwendung während der Radiotherapie von Kopf-Hals-Tumoren bzw. bei Ganzkörperbestrahlung zugelassen. Jedoch erlaubte das bessere Verständnis der Signalwege während der Strahlenantwort die Entwicklung einiger vielversprechender Arzneimittel, die entweder als Radikalfänger funktionieren oder Regulatoren von Zelltodwegen oder dem Zellzyklusarrest als spezifische Zielmoleküle besitzen. In diesem Review werden die wichtigsten Zielmoleküle für Radioprotektoren oder -mitigatoren, die sich gegenwärtig in der klinischen Prüfung befinden, beschrieben.

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P. Maier, F. Wenz, and C. Herskind state that there are no conflicts of interest.

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  1. Department of Radiation Oncology Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1–3, 68167, Mannheim, Germany

    Patrick Maier, Frederik Wenz & Carsten Herskind

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Correspondence to Patrick Maier.

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Maier, P., Wenz, F. & Herskind, C. Radioprotection of normal tissue cells. Strahlenther Onkol 190, 745–752 (2014). https://doi.org/10.1007/s00066-014-0637-x

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