JERUSALEM ¿ Cancer treatment could no longer be a high-risk hit-or-die game of statistics, if clinical trials prove the validity of a new method for determining the sensitivity of cancer cells to drugs. Today, cancer patients are routed into grueling radiation and chemotherapy regimens with type, dosages and length of treatment based solely on general statistical calculations related to the histological identification of the tumor, leading to an acknowledged error rate of more than 50 percent for some cancers. The method for determining chemosensitivity of cancer cells, based on the enzyme ornithine decarboxylse (ODC), was discovered in the laboratory of Uriel Bachrach, professor of molecular biology at the Hebrew University-Hadassah Medical School in Jerusalem.
¿ODC is a key enzyme for cell proliferation,¿ said Yongchun Wang, a Chinese oncologist pursuing a doctorate with Bachrach in Jerusalem. She told BioWorld International that DNA stability is essential for keeping cells healthy and dividing normally. ¿ODC is the key enzyme for synthesis of polyamines, which stabilize DNA. What makes this approach unique among the many attempts to evaluate chemosensitivity of cancer cells is that ODC works very early in cell cycle and the detection product has a very short half-life, so sorting of patients is very sensitive and very rapid, within one to two days.¿
The anticancer drug reactions are assessed in vitro on patients¿ own blood cells. ¿An in vitro test of chemosensitivity of cancer cells could help tailor treatment to the patient, increase the chance of recovery, reduce undesired side effects, and minimize the emergence of multiple drug-resistant (MDR) variants,¿ Bachrach said.
During the next few months, the method will be tested in clinical trials in China on 100 leukemia and 100 lymphoma patients. An agreement for trials in China has been signed by The Hebrew University of Jerusalem and the Shandong Academy of Medical Sciences in Jinan, China. In the meantime, Bachrach is examining its efficacy for patients with solid tumors.
¿Of course, application is easier for patients with blood cancers because the cells are already dispersed,¿ Bachrach said. ¿Now, to simplify the procedures for the detection and quantitation of ODC for patients with solid tumors, we developed a new luminescence-based in vitro assay of chemosensitivity. The test is extremely sensitive and permits the detection of 1 to 5 pmoles of putrescine (the product of ODC).¿
Bachrach, with fellow department member Anat Shayovits, discovered the applicability of ODC as a marker for determining sensitivity of cancer cells to various drugs. The primary method is simple: ODC catalyzes the formation of putrescine, which is expressed early in the cell cycle and has just a 15- to 30-minute half-life, disappearing from cancer cells when drug treatment in vitro is effective, and persisting if there is resistance to the drug being tested measured by quantitative immunohistochemistry.
Yehuda Assaraf, of the Technion-Israel Institute of Technology, helped in confirming the concept that ODC can serve as a marker of proliferation of cancer cells. Clinical studies were carried out by Yaacov Ashkenazi, of Shaare Zedek Hospital in Jerusalem, who tested lymphoma and leukemia patients.
A commercial biotechnology firm will be established April 1 in Jinan to facilitate the commercial side of the cooperation, manufacturing bioassay kits for testing the blood of cancer patients. ¿With these kits, a further 1,000 tests will be carried out within just a few months, in the hopes of gaining approval of the Chinese health authorities for widespread use of the kits,¿ said Bachrach.