Drugs Preventing New Blood Cell Formation Often Fail to Bolster Action of Chemotherapeutic Agents

In some cases, simultaneous treatment with a drug that blocks new blood vessel formation (an antiangiogenesis drug) slows down or prevents re-growth of the tumor, however, in other cases the anti-angiogenesis drug has no effect.

To determine why this happens, investigators from the University of Toronto (Toronto, ON, Canada) examined the effects of several drug combinations on the growth of breast cancer, pancreatic cancer, and small cell lung cancer tumors. They reported in the September 9, 2009, issue of the journal Cancer Cell that co-administration of the anti-angiogenic drug bevacizumab with the chemotherapeutic agent paclitaxel improved survival benefits for metastatic breast cancer and small cell lung cancer. In contrast, co-administration of bevacizumab with gemcitabine for treatment of pancreatic cancer did not increase the effectiveness of chemotherapy alone.

The researchers concluded that the contribution of the antiangiogenesis drug was dependent on the ability of the chemotherapeutic drug to induce mobilization of circulating endothelial progenitor cells (CEPs) from the bone marrow compartment. These cells are manipulated by the tumor for re-growth of blood vessels.

"Chemotherapy remains the most commonly employed form of systemic cancer treatment. However, although partial or complete shrinkage of tumor mass is frequently induced in chemotherapy-responsive tumors, survival benefits of such responses can be compromised by rapid re-growth of the drug-treated tumors,” explained senior author Dr. Robert S. Kerbell, professor of molecular and cellular biology at the University of Toronto. "Our results provide a new perspective regarding the impact that conventional chemotherapy can have on tumor angiogenesis and hence how combination with antiangiogenic drugs may amplify the antitumor effects of chemotherapy. Further, our findings provide a potential explanation of why not all chemotherapy drugs will necessarily have their efficacy enhanced by the addition of an anti-angiogenic agent when the mechanism involves blunting CEP mobilization acutely induced by the chemotherapy drug.”

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