Targeting bile duct cancer - meet Mitesh Borad, M.D.

Targeting bile duct cancer – meet Mitesh Borad, M.D.

By
Mayo Clinic Staff

May 7, 2019

The search for treatment targets for patients with bile duct cancer, also known as cholangiocarcinoma, has taken a 360 degree turn, offering new hope for patients. That’s according to Mitesh Borad, M.D., deputy director for Center for Individualized Medicine Biomarker Discovery Program at Mayo Clinic’s Arizona campus, Dr. Borad and his colleagues are using new genomic technologies and innovative approaches to data analysis to uncover genetic mutations driving the disease with the goal of developing new targeted therapies.

Genomics opens door to new treatment options

The bile duct is a network of tubes that connects the liver, gallbladder and small intestine. Each year, 6,000 patients in the U.S. are diagnosed with bile duct cancer. For years, there were limited treatment options for this rare cancer, with fewer than 10% of patients surviving for five or more years.

“In the past, rare cancers like bile duct cancer did not receive the attention or resources to help identify new treatments. As a result, the biology and genetics of this cancer were poorly understood. At the same time, there was a great unmet patient need for more precise therapies with fewer side effects,” explains Dr. Borad.

But over the last decade, Dr. Borad’s team has refined a framework now used around the country to open the door for new treatment options.

Using genetic testing on tissue samples from thousands of patients, the team searched for genetic mutations that may be driving the disease. They uncovered more than 25 genetic mutations that hold the potential to be treated with available targeted therapies or immunotherapies, which harness the power of the patient’s own immune system to fight their cancer.

The Mayo team has also shown that newly developed targeted therapies, known as fibroblast growth factor receptor (FGFR) inhibitors, can shrink bile duct tumors in patients who have mutations in certain FGFR genes.

“Our initial research in this area is now being validated in larger scale clinical trials, and we hope results will lead to approval for this new treatment approach,” says Dr. Borad.

Liquid biopsies – a simple blood test to detect, treat cancer sooner

Dr. Borad and his colleagues are also developing blood tests, known as liquid biopsies, to detect traces of DNA shed into the bloodstream from cholangiocarcinoma tumors.

As he explains, cholangiocarcinoma can be difficult to diagnose, depending upon where it is located. Frequently, the disease is not diagnosed until it has advanced and spread to other areas of the body.

“Because of the location of cholangiocarcinoma, it can be difficult to obtain a high quality tissue sample with a traditional biopsy. Liquid biopsies offer a faster, non-invasive and lower cost approach to detecting the early signs of cancer or cancer recurrence. They can also identify specific genetic mutations in a patient’s tumor that may be targeted with therapies.”

In one of the largest patient studies to date, the Mayo team used liquid biopsies to analyze tumors from 124 patients with cholangiocarcinoma.

“We identified several genes, 55% of which may have implications for treatment options. This could help patients avoid harmful side effects from an ineffective treatment,” says Dr. Borad.

The team’s next step is to compare the validity of these liquid biopsies against results from traditional tissue biopsies.

For Dr. Borad, this research has been rewarding. As a hematology and oncology fellow at Tulane University, he saw the need for developing new treatments for patients who did not respond to standard therapy or whose cancer returned after treatment.

Committed to finding answers, he spent three years as a Genomics Medicine Scholar at Translational Genomics Research Institute (TGen), joining Mayo Clinic in 2008.

“The new options for patients with bile duct cancer are a perfect example of how precision medicine can make a real difference. In fact, bile duct cancer is one of the gastrointestinal diseases most amenable to a precision medicine approach, offering individualized care based on a patient’s specific needs.”