Dr. Tom Flaig, center, withPre-treating an especially aggressive type of bladder cancer cell more than doubles the effectiveness of chemotherapy in culture, according to researchers at the University of Colorado Cancer Center.

Mesenchymal-type bladder cancer cells that tend to resist chemotherapy can be made more sensitive if pre-treated with vandetanib, a drug that has been clinically tested against thyroid cancer, according to the study published in the October 2010 issue of Oncology Reports (Volume 24, Number 4).

Mesenchymal cells are very aggressive and invasive, responsible for spreading cancer from the main site throughout the body. The current bladder cancer chemotherapy drug, cisplatin, does not kill these cells but can effectively treat epithelial-type cells that originate from the lining of the bladder, says Thomas Flaig, MD, assistant professor of medical oncology at CU Cancer Center whose team conducted this research.

“When we pre-treated mesenchymal bladder cancer cells and then looked at them under a microscope, they appeared more like epithelial cells and they responded much better to treatment,” Flaig says.

Bladder cancer is the sixth most common type of cancer, with more than 70,000 cases expected to be diagnosed this year, according to the National Cancer Institute. Yet it is one of the least researched cancers. “In the last decade, we have not changed the way we treat bladder cancer,” Flaig says.

Vandetanib works by inhibiting the VEGFR and EGFR growth pathways, causing the mesenchymal cells to become more chemosensitive, says Xiaoping Yang, PhD, a researcher in Flaig’s lab who also worked on this study. The key, however, is to pre-treat the cells as simultaneous treatment with both drugs was not effective.

The implication for this work is to develop customized cancer treatment unique to the make-up of the individual patient’s bladder cancer, Yang says. If a patient’s cancer is made up largely of mesenchymal cells, they would be pre-treated to make chemotherapy more effective.

“Everyone with bladder cancer now gets chemotherapy,” says Flaig, a treating medical oncologist who specializes in bladder cancer. “We believe that in the future, we’ll look at what kind of cells make up your cancer and customize treatment accordingly.”

This study was conducted on tissue cultures in the lab. The next step is to test the regimen in animal models. Because both drugs are currently in the clinic, clinical trials could occur in the near future if the next phase of testing is successful, Flaig says.