Bachrach Uriel
Department of Molecular Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Methods Mol Med. 2005;110:197-211. doi: 10.1385/1-59259-869-2:197.
The development of reliable methods for the in vitro testing of sensitivity of cancer cells to various drugs has been a longstanding objective in cancer treatment. The development of individualized chemotherapy could minimize undesired toxic side effects and increase the chance of recovery. The known methods for in vitro chemosensitivity tests are mainly based on monitoring the metabolic changes induced in cancer cells by the drugs. These experiments, as well as attempts to cultivate isolated cancer cells, did not give reliable results. In this study, I used a marker for proliferation to detect the effect of drugs on the potential of cancer cells to divide. An ideal marker should be present in all cells, be expressed early in the cell cycle, and have a short half-life. Ornithine decarboxylase (ODC), which catalyzes the conversion of ornithine to putrescine, fulfilled these prerequisites. Because ODC has an extremely short half-life, it disappears when cellular proliferation is arrested. The decay of ODC was assayed both by determining its activity and by immunohistochemical analyses. This approach was successfully used to determine the sensitivity of lymphocytes from hematological cancer patients to various drugs. It is conceivable that this method could serve as an important tool to improve cancer chemotherapy.
