New Drug Combination is Able to Eradicate Breast Metastases in Mice
News Dec 21, 2007
A novel combination of drugs was able to completely eradicate human breast metastases growing in mice, and shows promise for the effective treatment of patients with advanced metastatic breast cancer.
Dr. Sophia Ran from Southern Illinois University School of Medicine presented the results of a study using nab-paclitaxel and bevacizumab to treat lymphatic and pulmonary metastases in female SCID mice.
Paclitaxel is a widely used cancer chemotherapy drug, originally derived from an extract of the yew tree. It can have severe side effects, some of which are related to the fact that it will not dissolve in water and has to be dissolved in organic solvents for injection. Nab-paclitaxel is a nanoparticle form of paclitaxel that is coated with a nonreactive protein, albumin, allowing it to be dissolved in water. This has reduced the side effects of the treatment, and also makes it more effective.
Bevacizumab is a monoclonal antibody against vascular endothelial growth factor A (VEGF-A), a protein that is involved in building new blood vessels. Tumors require new networks of blood vessels in order to grow.
The idea for this research came from the observation that, nf cells that survive treatment with chemotherapy, the stress of the treatment causes excess VEGF-A to be produced.
The VEGF-A protects the cells against future chemotherapy, and also generates new blood vessels. Both mechanisms may contribute to tumor recurrence and metastatic spread following chemotherapy. This is the molecular basis for combining bevacizumab with nab-paclitaxel for the treatment of metastatic tumors.
For this study, human breast cancer cells were implanted into mammary fat pads (the mouse equivalent of breast tissue) of female mice. The implanted cells grew into tumors, and lymphatic and pulmonary metastases developed by the time that the drugs were administered.
The drug combination completely eradicated the original tumors, although bevacizumab alone had no effect, and nab-paclitaxel alone caused tumor regression for only 27 days, after which the tumors grew back.
The drug combination also completely eradicated metastases in the treated animals. Bevacizumab alone and nab-paclitaxel alone reduced the average number of metastases by no more than 50%.
The combination of bevacizumab and nab-paclitaxel is currently being tested in early trials of women with metastatic breast cancer.