Drug Combo for Pancreatic Cancer

Researchers at Rutgers University (NJ, USA) have been able to halt prostate cancer in laboratory animals using a compound derived from a Southeast Asian shrub known as TPA, together with all-trans retinoic acid (ATRA), a vitamin A derivative previously shown to treat leukemia.

"Pancreas cancer is a tough one to treat,” said Allan H. Conney, professor of chemical biology at Rutgers. "Treatment options are very limited, and not many people survive. TPA has good potential for therapy, so it's definitely worth pursuing.”

Encouraged by their progress, the researchers initiated studies with the pancreas, using three human pancreatic cancer cell lines with different molecular properties. In lab cultures, they applied TPA to cells from these lines and found that growth of the pancreatic cancer cells was inhibited by TPA in levels that should not be toxic to patients.
The researchers also tested TPA on the cells in combination with ATRA. "We found that the TPA/ATRA combination in cell culture worked better than the individual compounds alone,” said Dr. Conney

The scientists then injected cells from the human cancer cell lines into immunodeficient mice to grow pancreatic tumors against which the compounds could be tested. After they began treating the mice with TPA alone and in combination with ATRA, they observed inhibition of tumor growth and reduction in tumor size. There was a substantial increase in apoptosis and a substantial decrease in mitosis in the tumors.

"We were simultaneously stopping the growth of new cancer cells and killing those already existing,” noted Dr. Conney. "This was most dramatic when we used the TPA/ATRA combination on the tumors.” He added that increased efficacy of the potent combination would permit even lower doses to be used. The research findings are to be reported in the October 2005 issue of The Journal of Pharmacology and Experimental Therapeutics.






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