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Genomic sequencing used to help identify new therapies for bile duct cancer

Date:
February 13, 2014
Source:
Mayo Clinic
Summary:
Physicians have personalized drug treatments for patients with cholangiocarcinoma using genomic sequencing technologies. Potential new treatment approaches are being validated to develop new tests that physicians can use to guide therapy for this aggressive cancer of the bile ducts that progresses quickly and is difficult to treat.

A patients' tumors from cholangiocarcinoma, a rare liver cancer that typically fails chemotherapy, shrunk significantly after treatment with FGFR inhibitors, which were prescribed based on results of next generation sequencing. The drugs used, pazopanib (top) and ponatinib, are typically used to treat kidney cancer and certain types of leukemia, respectively.
Credit: Image courtesy of Mayo Clinic

Physicians at Mayo Clinic’s Individualized Medicine Clinic and researchers at the Translational Genomics Research Institute (TGen) have personalized drug treatments for patients with cholangiocarcinoma using genomic sequencing technologies. Potential new treatment approaches are being validated to develop new tests that physicians can use to guide therapy for this aggressive cancer of the bile ducts that progresses quickly and is difficult to treat.

Clinically important findings suggest that targeting the epidermal growth factor receptor (EGFR) and the fibroblast growth factor receptor (FGFR) cellular pathways may benefit thousands of patients with this disease, according to the study published today in the journal PLOS Genetics.

Half of the patients treated in this study responded to either ponatinib (typically used for certain types of leukemia) or pazopinib (a kidney cancer drug), depending on the genetic alterations identified through sequencing.

“In 3 out of the 6 patients we analyzed, we found compelling, treatable and unexpected genetic alterations that would never have been found by normal testing methods for cholangiocarcinoma,” says Mitesh Borad, M.D., a Mayo Clinic oncologist and lead author of the paper. “We treated these three patients with drugs that attack these genetic alterations and saw tumor shrinkage. This gives us hope for better treatments for this aggressive, hard-to-treat cancer.”

Because of these encouraging early results, the team of 49 doctors and researchers proposes large-scale clinical trials to test EFGR and FGFR inhibitors as possible treatments for biliary tract cancers that harbor mutations in these genes and pathways.

“Our results demonstrate that if we find the right molecular context, more appropriate therapies can be chosen that improve outcomes,” says John Carpten, Ph.D., TGen deputy director of basic science and director of TGen’s Integrated Cancer Genomics Division, and the study’s senior author. “We now hope to design larger clinical studies to treat patients’ tumors harboring these novel genomic aberrations to further explore the precise extent of clinical benefit for patients with primary or advanced cholangiocarcinoma.”

Bile duct cancer is a rare cancer that occurs mostly in people older than age 50. Surgical approaches, such as resection and liver transplantation, represent the only curative treatment approaches, says Dr. Borad. Most patients, however, present with surgically unresectable or metastatic disease at the time of diagnosis. Standard-of-care chemotherapies are not curative and there is an unmet need for newer approaches, Dr. Borad adds.


Story Source:

The above story is based on materials provided by Mayo Clinic. Note: Materials may be edited for content and length.


Journal Reference:

  1. Mitesh J. Borad, Mia D. Champion, Jan B. Egan, Winnie S. Liang, Rafael Fonseca, Alan H. Bryce, Ann E. McCullough, Michael T. Barrett, Katherine Hunt, Maitray D. Patel, Scott W. Young, Joseph M. Collins, Alvin C. Silva, Rachel M. Condjella, Matthew Block, Robert R. McWilliams, Konstantinos N. Lazaridis, Eric W. Klee, Keith C. Bible, Pamela Harris, Gavin R. Oliver, Jaysheel D. Bhavsar, Asha A. Nair, Sumit Middha, Yan Asmann, Jean-Pierre Kocher, Kimberly Schahl, Benjamin R. Kipp, Emily G. Barr Fritcher, Angela Baker, Jessica Aldrich, Ahmet Kurdoglu, Tyler Izatt, Alexis Christoforides, Irene Cherni, Sara Nasser, Rebecca Reiman, Lori Phillips, Jackie McDonald, Jonathan Adkins, Stephen D. Mastrian, Pamela Placek, Aprill T. Watanabe, Janine LoBello, Haiyong Han, Daniel Von Hoff, David W. Craig, A. Keith Stewart, John D. Carpten. Integrated Genomic Characterization Reveals Novel, Therapeutically Relevant Drug Targets in FGFR and EGFR Pathways in Sporadic Intrahepatic Cholangiocarcinoma. PLoS Genetics, 2014; 10 (2): e1004135 DOI: 10.1371/journal.pgen.1004135

Cite This Page:

Mayo Clinic. "Genomic sequencing used to help identify new therapies for bile duct cancer." ScienceDaily. ScienceDaily, 13 February 2014. <www.sciencedaily.com/releases/2014/02/140213184651.htm>.
Mayo Clinic. (2014, February 13). Genomic sequencing used to help identify new therapies for bile duct cancer. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2014/02/140213184651.htm
Mayo Clinic. "Genomic sequencing used to help identify new therapies for bile duct cancer." ScienceDaily. www.sciencedaily.com/releases/2014/02/140213184651.htm (accessed July 25, 2014).

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