Efforts to enhance the effect of radiation therapy. Mechanism of action and clinical application of radiation sensitizers

Efforts have been made to enhance the effect of radiation therapy by means of reducing the radiation sensitivity in normal tissues and of increasing the sensitivity in tumors. Since the target of radiation is DNA, direct sensitizing can be expected for DNA-injuring chemicals like bleomycin, pepleomycin, alkylating agents, mitomycin and platinum complexes. Sensitization can be also possible by inhibiting the nucleic acid synthesis: inhibitors like ribonucleotide reductase, pyrimidine and purine analogs and folate analogs. Angiogenesis inhibitors and oxygenating agents, by altering the circumstances in the tumor tissues, can be a sensitizer. Cytocidal effect of radiation is enhanced by inhibiting the DNA repair: inhibitors of poly(ADP-ribose) polymerase and topoisomerases. Biological response modifiers are used to reduce the adverse effects. Inhibitors of protein kinase C and A are also the sensitizer inhibiting the intracellular signal transduction. Development of a better sensitizer is expected. (K.H.)