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.

Treatment of hepatocellular carcinoma (HCC) is a major concern for physicians as its response to chemotherapy and radiotherapy remains generally poor, due, in part, to intrinsic resistance to either form of treatment. We previously reported that an irradiation with fast neutrons, which are high-linear energy transfer (LET) particles, massively induced autophagic cell death in the human HCC SK-Hep1 cell line. In the present study, we tested the capacity of the mammalian target of rapamycin (mTOR) inhibitor RAD001 to augment the cytotoxicity of low and high-LET radiation in these cells. As mTOR is a key component in a series of pathways involved in tumor growth and development, it represents a potential molecular target for cancer treatment. Results indicate that RAD001, at clinically relevant nanomolar concentrations, enhances the efficacy of both high- and low-LET radiation in SK-Hep1 cells, and that the induction of autophagy may account for this effect. However, fast neutrons were found to be more efficient at reducing tumor cell growth than low-LET radiation.

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A total of 48 patents/applications were selected. These concerned agents target molecular components of pathways involved in DNA damage repair, cell growth and survival signalling, apoptosis modulation and tumour angiogenesis. Current trials of some of these agents may reveal their value as clinical radiosensitisers.

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