Researchers use genistein to improve outlook of pancreatic cancer

Barbara Ann Karmanos Cancer InstituteApr 20 2010

Scientists at the Barbara Ann Karmanos Cancer Institute in Detroit today presented data at the American Association for Cancer Research's 101st Annual Meeting 2010 that shows when genistein, a component of soy, is paired with the FDA-approved drug oxaliplatin, pancreatic cancer cells become more sensitive to chemotherapy.

The title of the poster presentation is, "Genistein restored chemosensitivity to oxaliplatin in gemcitabine resistant pancreatic cancer cells in vitro and in orthotopic xenograft mouse model."

Researchers are hopeful that this naturally-occurring agent will improve the outlook of pancreatic cancer, which is particularly hard to treat, according to Fazlul Sarkar, Ph.D., professor of pathology at Karmanos Cancer Institute and Wayne State University School of Medicine, as well as study co-author. Only 15 percent of pancreatic tumors are surgically removable and about 20 percent of patients who undergo surgery survive five years after the treatment. The average survival of patients with more advanced disease is only six months. About 37,000 people succumb to pancreatic cancer annually.

Chemotherapy remains the most common form of treatment for pancreatic cancer, with the drug gemcitabine showing very modest benefits. Oxaliplatin is a commonly used therapy that is paired with gemcitabine, but studies have shown that benefits were offset by the rapid development of resistance by cancer cells against oxaliplatin.

"We are trying to see if we can make oxaliplatin a better drug for patients with pancreas cancer," Dr. Sarkar said. "We are hopeful that this study will be useful to design newer therapies for patients with pancreas cancer."

Researchers have shown in vitro and in orthotopic xenograft mouse models that by pre-treating pancreatic cancer cells with genistein and then using low concentrations of oxaliplatin, the viability of those cancer cells is significantly reduced and cell death is increased. Researchers also found that spread of the cancer cells to lymph nodes surrounding the pancreas was reduced.

Dr. Sarkar and his research colleagues have devoted approximately 15 years to studying naturally-occurring agents. In past studies, they have paired genistein with gemcitabine for the treatment of pancreatic cancer, and docetaxel, a treatment for prostate cancer, and demonstrated increased sensitivity in those cancers to traditional drugs. They also studied the anti-cancer effects of various natural agents such as soy isoflavones; curcumin, a derivative of tumermic; indole-3-carbinol, found in green leafy vegetables; resveratrol, found in grapes and red wine; and polyphenols found in green tea.

"We are trying to understand the mechanism of action of natural agents, and then test them out in an animal model to confirm their anti-cancer activity," said Dr. Sarkar, "We also test whether natural agents could sensitize tumor cells to conventional therapies such as chemotherapy and radiation treatment. We then plan to translate our findings into newer therapies that can be tested in patients by performing clinical trials.

"We have made significant progress in all three areas."

Researchers are now looking at moving their findings to clinical trials to test whether genistein pre-treatment with the use of oxaliplatin in patients with pancreatic cancer could be more effective. They also have two patents pending for the creation of synthetic analogs, one for isoflavones and another for curcumin, which were studied in the treatment of colon and pancreatic cancers.

"We were the first to show that many natural agents can sensitize tumor cells to conventional therapies," Dr. Sarkar said.