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News/ Breakthroughs

Groundbreaking Chemotherapy Regimens Make Pancreatic Tumors Operable

Pancreatic cancer is known to resist chemotherapy, forcing oncologists to use second and third lines of defense. To meet this challenge, Robert Fine, MD, Herbert Irving Associate Professor of Medicine, an oncologist who works with the Pancreas Center to treat its patients, has developed several multiple-drug chemotherapy regimens.

• Developed by Dr. Fine's laboratory, the GTX chemotherapy regimen consists of three drugs — Gemzar, Taxatere, and Xeloda — and is currently in Phase II clinical trials. As a first-line therapy for advanced pancreatic cancer, GTX is routinely combined with radiation to shrink tumors so that they are operable. Dr. Fine calls GTX a "smart" regimen because it circumvents mechanisms of drug resistance by specifically inhibiting pathways active in pancreatic cancer. Of all the options available today, GTX has produced the highest response rates (40%) and rates of survival in the U.S. and Europe in early studies.
• Dr. Fine's laboratory found that pancreatic cancer cells can become resistant to GTX by activation of specific signaling pathways called MAPK. In response, the team developed a specific sequence of the drugs that inhibits this activation and leads to the death of cancer cells. Clinical studies to date show that approximately 40% of GTX failures can be salvaged by this chemotherapy regimen.
• The team has also created and perfected two novel therapies in their laboratory that will enter testing in pancreatic cancer patients in the near future. One is a gene therapy approach which selectively targets cells with mutations that occur in many pancreatic cancers. The other is a peptide that selectively binds to mutated proteins found in pancreatic cancer cells and then restores them back to a normal state, resulting in cell death. If the peptide is delivered endoscopically into the pancreatic duct, where 95% of all pancreatic cancers develop, it may be possible to eradicate pre-malignant pancreatic growths which contain this mutation (approximately 75%). Both novel therapies will be tested in patients with PET and CT scans.