Drugs Succeed by Attacking Prostate Cancer Indirectly

Researchers have found that a drug combination that fails to kill prostate cancer cells growing in tissue culture is effective in an animal model due to its ability to destroy the epithelial cells that supply blood and nutrients to the developing tumor.

Investigators at the University of Texas M.D. Anderson Cancer Center (Houston, USA) developed a multi-drug resistant line of prostate cancer cells by growing them in culture with increasing concentrations of the chemotherapeutic agent paclitaxel. The resistant cells were implanted into one tibia of 80 nude mice. Two weeks later, the mice were randomly assigned to receive distilled water (control group), paclitaxel, the platelet-derived growth factor receptor (PDGFR) kinase inhibitor imatinib, or imatinib plus paclitaxel for 10 weeks (20 mice per group).

Tumor incidence and weight, bone structure preservation and osteolysis, and the incidence of lymph node metastasis were determined. The phosphorylation status of PDGFR on tumor cells and tumor-associated endothelial cells and levels of apoptosis were examined with immunohistochemical analyses. Microvessel density was assessed as the number of cells expressing CD31/platelet endothelial cell adhesion molecule 1 (PECAM-1).

Results published in the June 7, 2006, issue of the Journal of the National Cancer Institute revealed that only four of 18 mice treated with the combination developed tumors. Median tumor weight for this group was one tenth of a gram, and the cancer spread to the lymph nodes in three cases. In contrast, tumors grew in all 19 control mice, their median tumor weight was 1.3 grams, and all metastasized to the lymph nodes.

"Why, then, did it work so well in the animal? Because we did not attack the tumor, we attacked the blood vessels. We target and destroy the vasculature that provides oxygen and nutrients to tumor cells,” said senior author Prof. Isaiah J. Fidler, director of cancer metastasis research at the M.D. Anderson Cancer Research Center.



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University of Texas M.D. Anderson Cancer Center