Pancreatic cancer is currently incurable. It is resistant to all known cancer treatments, including chemotherapy. Recent research may help change that. Chemotherapy has not been successful of chemotherapy resistance, much of which appears to be the result of an enzyme called TAK−1. A recent study has found that by deactivating this enzyme, researchers were able to kill pancreatic cancer cell lines with low doses of chemotherapeutic agents. The same strategy allowed the researchers to shrink pancreatic tumors in mice, lengthening their lives.

The combination shrank the size of pancreatic tumors by up to 78% and increased the average survival of the mice from 68 to 122 days.

The issue of chemotherapy resistance is important because pancreatic cancer cells can be killed in the laboratory with standard chemotherapy drugs, but the doses required are way too high to even consider using them in humans. Researchers at the M. D. Anderson Cancer Center in Houston, Texas had been studying the role of the enzyme TAK−1 in the development of pancreatic cancer. They developed a drug which blocked TAK−1 and found that it lowered the cancer cells' resistance to chemotherapeutic drugs. In the presence of TAK−1 inhibitor, doses of three standard chemotherapy agents (gemcitabine, oxaliplatin and SN−38) could be reduced up to 70−fold and still kill the same number of cancer cells. This suggested that the same approach might work in animals and humans.

The researchers then tested the TAK−1 inhibitor in mice, in combination with a very low dose of the chemotherapy drug gemcitabine, a dose that would have been ineffective on its own. The combination shrank the size of pancreatic tumors by up to 78% and increased the average survival of the mice from 68 to 122 days.

The researchers plan to test whether the TAK−1 inhibitor can also lower the required dose of other chemotherapy drugs down to non−toxic levels in mice. They ultimately hope to conduct clinical trials in humans.

Considering that there is no currently effective treatment for pancreatic cancer, any treatment that helps would be welcome.

The research was presented September 24, 2009 in Berlin, at Europe's largest cancer conference, held jointly by the European Cancer Organization and the European Society for Medical Oncology (ECCO−ESMO). It was presented by Dr. Davide Melisi, formerly a fellow at the Anderson Center and currently a staff member of the National Cancer Institute in Naples, Italy.