The CancerWeb Report, What's New In Cancer: November, 1996
Colorectal Cancer

• Genetic therapy using p53 to potentiate chemotherapy? - The so-called wild-type p53 is expressed in reaction to damage to DNA. It suppresses cancer development, either by inducing a pause in the cell cycle, which allows DNA repair to occur, or by initiating apoptosis, programmed cell death, each of which events eliminates the danger of an abnormal cell being propagated. As discussed under Breast Cancer in this month's CancerWeb Report, abnormal expression (loss or abnormal form) of p53 may be linked to development of human cancer, not only of the breast, but also of other cancers, most notable of the bladder and colon. About 70% of human colon cancers have lost or altered p53. In an article in the October, 1996 issue of Clinical Cancer Research, researchers from Case Western Reserve University in Cleveland, used genetic engineering techniques to insert a wild-type p53 gene into colon cancer cell lines. This gene, when induced by a chemical did not cause apoptosis, but did permit these cells to undergo growth arrest. Two cell lines in which the wild-type p53 was induced showed 10- and 40-fold increases in radiosensitivity, 24- and 38-fold increases in sensitivity to 5-fluorouracil (5-FU), and 4- and 7-fold greater sensitivity to topotecan. Although the gene by itself did not induce apoptosis, additional experiments indicated that it did enhance the induction of apoptosis by 5-FU. These results suggest that clinical resistance to chemotherapy drugs may be caused by loss of p53, and that inducing the wild-type gene by genetic engineering might enhance the effects of chemotherapy and radiation. (Yang, Clin Cancer Res 2:1649, 1996)

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• Western-style diets produce precancerous changes in rodent colons - Western-style diets, with high levels of fat and phosphate and depleted in calcium and vitamin D, produced and areas with abnormal cells and precancerous growth features when fed to mice for 2 years. This study in the November 1, 1996 issue of Cancer Research was carried out in Turin, Italy, and the Strang Cancer Prevention Center in New York. (Risio, Cancer Res 56:4910, 1996)

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• An intensified treatment based on timed delivery of chemotherapy - In recent years it has been found that such features as the metabolism and toxicity of chemotherapy drugs varies in a daily rhythm, reflecting reproducible daily changes in the body. The technique of making use of these rhythms to improve chemotherapy has been called chronotherapy. An article by researchers at the Cancer and Immunogenetics Institute in Villejuif, France, who applied this technique to colon cancer, appeared in the November, 1996 issue of the Journal of Clinical Oncology. They gave a three-drug combination of 5-fluorouracil, leucovorin, and oxaliplatin, over 4 days by a time-modulated process using a programmable pump. This was repeated every 14 days. Peak flow of drug was timed to occur at 4:00 p.m. for oxaliplatin and at 4:00 a.m. for 5-fluorouracil; the dose of the latter was also adjusted for toxicity. Response rates were 40% in 37 previously treated patients and 69% in 13 who were untreated. Regression of tumor permitted residual metastases to be removed in 26% of patients. This approach deserves more extensive testing. (Bertheault-Cvitkovic, J Clin Oncol 14:2950, 1996)