Reversed-role chemotherapy for resistant cancer.

Chemotherapeutic agents that have come into clinical use because of their selective effect against cancers have limited success mainly because many cancer cells become resistant to them. Some chemotherapeutic agents inhibit DNA synthesis in normal cells but not in tumour cells so that nucleoside analogues with cell-killing potential can be incorporated into cancer cells when they continue to synthesise DNA in the presence of agents that stop DNA synthesis in normal cells. The potential of halogenated pyrimidines as sensitisers of cancers to ionising and photo-irradiation might be extended by giving them with agents that inhibit their uptake by normal tissues. A similar approach might also be used with conventional cytotoxic chemotherapy. Radiolabelled pyrimidine analogues may have a role in treating tumours resistant to inhibitors of DNA synthesis. They may also prove useful agents for gamma-camera imaging when normal tissue uptake is blocked.