| abstract |
The present invention is related to agents useful in the treatment of tumors by radiation by sensitizing tumor cells toward the radiation. The agents of the invention can perform selective tumor radiosensitization and be involved in tumor directed hypomethylation. The agents of the invention include (a) 5-chloro-2'-deoxycytidine (CldC) administered without a cytidine deaminase inhibitor, (b) CldC administered with a cytidine deaminase inhibitor, (c) CldC and 4-N-methylamino 5-fluoro-2'-deoxycyxtidine (4-N-methylamino FdC), or (d) CldC and 4-N-methylamino FdC coadministered with a cytidine deaminase inhibitor. The cytidine deaminase inhibitor can be tetrahydrouridine or Zebularine. Within the scope of the invention are methods of treating tumors by administering the agents of the present invention without the need of other modulators of metabolism. Another aspect of the invention is a method of hypomethylating a gene silenced in a tumor of a subject by administering the agents of the invention to the subject to reduce the aggressiveness of the tumor, the metastatic propensity of the tumor, the genetic instability of the tumor, and/or the resistance of the tumor to drug or radiation treatment. An additional aspect of the invention is a method of protecting normal tissues during a radiation treatment of a tumor in a subject by administering the agents of the invention to the subject before or during the radiation treatment. The agents of the invention can be combined with new sources or new schedules of radiation, and new categories of tumors can also be treated with the agents of the invention. |