Radiosensitising agents for the radiotherapy of cancer: advances in traditional and hypoxia targeted radiosensitisers

Author： Bischoff Pierre Altmeyer Anais Dumont Francis

ISSN： 1354-3776

Source： Expert Opinion on Therapeutic Patents, Vol.19, Iss.5, 2009-05, pp. : 643-662

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Abstract

Background: Radiotherapy is utilised for the treatment of ∼ 50% of patients with solid tumours, but its efficacy is limited by normal tissue toxicity and by the intrinsic or acquired radioresistance of many tumours. The combination of radiotherapy with chemotherapeutic agents that preferentially sensitise tumour cells to its cytotoxic effects has thus long been considered as a strategy to enhance cancer therapy. However, current chemoradiotherapy protocols remain highly unsatisfactory. Therefore, continuing efforts are being conducted to identify improved radiosensitising agents. Objective: To survey the patent literature and associated peer-reviewed publications of the past 4 years pertaining to the development of novel radiosensitising agents, with a focus on anticancer drugs traditionally used as radiosensitisers and on agents targeting radioresistant hypoxic tumour cells. Methods: Patents were searched with a set of relevant keywords using several search engines (ep.espacenet.com/, www.freepatentsonline.com/, patft.uspto.gov/). A Medline search on the same topics was performed in parallel. Results/conclusion: A total of 37 patents/applications were retrieved. Of these, 14 concern the use of conventional anticancer cytotoxic drugs for tumour radiosensitisation. The other patents mostly disclose novel hypoxic radiosensitisers, bioreductive drugs and inhibitors of hypoxia-inducible factor-1. Whether these advances will translate into clinically valuable radiosensitisers is, however, unclear.