Anti-Hormonal Approach to Leukemia¿Radioactive Ligand

Approximately half of the individuals diagnosed with cancer will die of the disease even if they receive the best therapies that modern medicine has to offer. In addition, even with current therapies, including surgery, radiation, and chemotherapy induced remission, the side effects are ravaging and reduce "quality of life" to an unacceptable level. Obviously, new therapeutic approaches are needed which are more specific, less damaging and more effective. Several years of leukemia research has led the principal investigator to a hypothesis that many cancers remain hormone-dependent, retain the ability to terminally differentiate, and exhibit many normal cell properties. The present study was initiated to exploit on of these properties, namely hormone sensitivity of leukemia cells, in an effort to develop a lineage specific, gentle, safe and effective drug which will destroy leukemia cells. In particular, a radioactive drug will be devised which will specifically bind erythropoietin receptors on erythropoietin-dependent leukemia cells, and in doing so will deliver a killing dose of radiation to the tumor. In Phase I, we will construct the radioactive hormone and test its binding, internalization and killing power on Epo- dependent cell lines. If feasibility of this approach is confirmed, Phase II will attempt to prove the efficacy of radioactive ligands to destroy selected leukemia in the animals.