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June 1st, 2016

Researchers Identify Best Drug Therapy for Rare, Aggressive, Pancreatic Cancer

By Jeff Briggs

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Genomic research and the application of individualized medicine are wide-spread throughout Mayo Clinic. The ability to collaborate in teams helps drive discovery, translation and application of medical breakthroughs. We are unrelenting in our search for new solutions. Right now, there are over 11,000 human studies under way across Mayo for devastating health conditions, and many of them involve genomic research.  As you might imagine, not all of them are conducted through the Center for Individualized Medicine, but as regular readers of the blog know, we like to highlight from time to time the great work some of our colleagues are doing in genomic medicine.  Here is news about the discovery of a new drug therapy for pancreatic cancer.

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Researchers Identify Best Drug Therapy for Rare, Aggressive, Pancreatic Cancer

Each year, about 200 to 400 Americans develop pancreatic acinar cell carcinoma, a rare form of pancreatic cancer that has no effective standard of care. A study involving researchers on Mayo Clinic’s Florida and Rochester campuses has found that the chemotherapy drug oxaliplatin is effective in stopping the growth of this cancer. Their discoveries were published May 10 in the Journal of Translation Medicine.

Dr. John Copland

Dr. John Copland

Researchers used tumor tissue biopsied from a patient whose cancer spread to the liver to develop the first patient-derived tumor xenograft, or avatar mouse model, which enabled testing of a number of drugs.

Oxaliplatin stopped tumor growth after only three treatments, and the tumor did not grow back after treatment ended.

“We showed the tumor growth was inhibited by a number of drugs, but oxaliplatin was the standout drug,” says John Copland, III, Ph.D., a cancer biologist and the study’s principal investigator. “Our hope is that information gleaned from our study will provide new options for patients diagnosed with this rare form of cancer.”

Patients live an average 49 months after being diagnosed with pancreatic acinar cell carcinoma. They only live about 14 months once the cancer has spread, or metastasized.

Oxaliplatin inserts itself into DNA, which results in the death of multiplying tumor cells — particularly if those cells carry a DNA repair mutation. The study found that the patient tumor used in this research had a mutation in the DNA repair gene BRCA-2.

Dr. Gerardo Colon-Otero

Dr. Gerardo Colon-Otero

This indicates physicians may want to test patients with pancreatic acinar cell carcinoma for DNA repair gene mutations to provide a more highly individualized medicine approach toward treatment.

“This may be a breakthrough for this rare cancer,” says Gerardo Colon-Otero, M.D., an oncologist and study co-author. “Genomic testing for DNA mutations can now be performed, and, if the results are positive, those patients are candidates for platinum-based drugs, such as oxaliplatin.”

Lead author Jason Hall, Ph.D., a Mayo Clinic research fellow, also showed that the tumor began to re-express markers of normal pancreas tissue.

“This is most likely the explanation for the very prolonged response,” says Dr. Hall. “Perhaps we should explore more chemotherapy drugs that can kill cancer cells as well as revert them to a more normal state.”

Dr. John Copland discusses the best drug therapy for rare, aggressive pancreatic cancer.

Additional Mayo Clinic study co-authors are:

Additional co-authors are:

  • Adam C. Mathias, B.S., of Delta Synthetic Co., Ltd.
  • Louis K. Dawson, B.S.; William F. Durham, M.S.; Robert J. Mullin, Ph.D.; Aidan J. Synnott, Ph.D.; Daniel L. Small, Ph.D.; Julia Schüler, Ph.D. ,Kenneth A. Meshaw, Ph.D.; of Charles Rivers Discovery Services
  • Daniel von Hoff, M.D., of TGen

The study was supported in part by National Institutes of Health/National Cancer Institute Grant R01CA136665 (Dr. Copland) and a generous gift from a grant for Rare Cancers from Dr. Ellis W. and Dona Brunton (Dr. Colon-Otero and Dr. Copland).

Competing interests:

  • Copland and Marlow received royalties from the patient-derived tumor xenograft model licensed to Charles River Laboratories International, Inc.
  • Mathias was an employee of Charles River Laboratories International, Inc., and now is employed by Delta Synthetic Co., Ltd.

 

Tags: BRCA-2, center for individualized medicine, Dr. Gerardo Colon-Otero, Dr. Jason Hall, Dr. John Copland, genomic medicine, Genomic Research, mayo clinic, oxaliplatin, Pancreatic Cancer, Uncategorized

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