Antiangiogenic Drugs' Role in Cancer Explored

Some chemo drugs cause rise in circulating endothelial progenitors, which can help tumors regrow

THURSDAY, Sept. 11 (HealthDay News) -- Circulating endothelial progenitors (CEPs) from bone marrow can contribute to the regrowth of chemotherapy-treated tumors, but combining chemotherapy with antiangiogenic drugs may inhibit this recovery, according to research published in the Sept. 9 issue of Cancer Cell.

Yuval Shaked, Ph.D., of the University of Toronto in Ontario, Canada, and colleagues investigated whether conventional chemotherapy drugs can induce CEP mobilization and help tumors recover. They found that in mice, some drugs (such as paclitaxel) caused acute CEP elevations within 24 hours, while others (such as gemcitabine) did not. In another experiment, the antiangiogenic drug DC101, given before treatment with paclitaxel, resulted in a smaller CEP spike in mice.

Further work in C57BL/6 mice given injections of Lewis lung carcinoma cells suggested that giving an antiangiogenic drug just before a chemotherapy drug that can induce a rapid CEP spike leads to improved treatment efficacy, but little improved antitumor activity is seen when it is combined with a chemotherapy drug that doesn't cause a CEP spike, the authors write.

"Our results raise a number of important questions relevant to antiangiogenic drugs and the role of CEPs in tumor angiogenesis," the authors write. "For example, as antiangiogenic small-molecule oral receptor tyrosine kinase inhibitors (RTKIs), which target multiple RTKs including VEGF receptors, have not yet shown an ability to enhance the efficacy of conventional chemotherapy in phase III trials, in contrast to bevacizumab, could this be due to an inability of such drugs to block CEP mobilization?"

ImClone Systems Inc. provided support for the study, and two of the study co-authors are employees of the company.

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