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April 25, 2025/Cancer/News & Insight

Molecular Insights into Early-Onset Biliary Tract Cancer (Podcast)

A call for awareness about the importance of genomic testing

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Early-onset biliary tract cancer is on the rise, but to date, little is known about the biology of the disease.

There's also a large paper in one of the Lancet journals from a couple of weeks ago showing that early onset cancers are rising across different types of cancers, and in different countries, so it’s definitely a worldwide public health issue,” says Alok Khorana, MD, Director of the Gastrointestinal Malignancies Program at Cleveland Clinic Cancer Institute.

In a recent episode of Cleveland Clinic’s Cancer Advances podcast, Dr. Khorana discussed:

• What defines early-onset cancer
• Microbiomic profiling his research team is studying
• Understanding molecular differences in young- and average-onset patients

Click the podcast player above to listen to the episode now, or read on for a short edited excerpt. Check out more Cancer Advances episodes at clevelandclinic.org/podcasts/cancer-advances or wherever you get your podcasts.

Excerpt from the podcast:

Dale Shepard, MD, PhD: When you look at these molecular differences, did you note any findings that you found between the two and any surprises in those?

Alok Khorana, MD: One of the big findings that we found was that FGFR2 fusion was much more common in the younger onset population. And this I think if I might use a call for awareness about the importance of genomic testing in the biliary tract cancer population.

For many years, these types of cancers were sort of considered an orphan illness, relatively rare, not a lot of understanding of what's driving it, not as much interest in investigating it. But over the past maybe five to seven years, it turned out that biliary cancers are a very, what we call a target-rich population. There's a lot of mutations that seem to occur in patients with biliary tract cancer that are druggable, so that have medications that can target those mutations.

And a good sort of rule of thumb is that somewhere between 30 and 40% of the biliary tract cancer population has something druggable, so FGFR fusions, for instance, IDH mutations, MSI high. Some are tumor agnostic, so they occur in all different types of cancers, but FGFR and IDH specifically are pretty druggable in the biliary tract cancer population. So those were some of the targets we tried to understand between the younger-onset and average-onset population.

And we found that FGFR2 fusion was significantly more prevalent in the younger population compared to the usual onset population. And that's really important, because of all the druggable targets in biliary tract cancer, FGFR fusion is probably number one. So there's already a bunch of drugs that target this specific alteration.

A couple are approved and a couple more are in development and likely to be approved. If there's one takeaway from all of this, it’s just make sure you get NGS testing on your biliary tract cancer patients, because you might be missing out on a bunch of therapeutic options if you don't.

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