Supriya Saha, oncologist and liver cancer researcher

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Supriya Saha, oncologist and liver cancer researcher

Asking important questions about a unique cancer

Dr. Supriya “Shoop” Saha is perhaps the only researcher in the world who is devoting his lab exclusively to untangling intrahepatic cholangiocarcinoma, or ICC.

ICC is not just a mouthful. It’s also a little-known, understudied and difficult-to-detect form of liver cancer that’s increasing in incidence worldwide. With no available early-detection or screening methods, patients are usually diagnosed only after their disease has begun to spread through their bodies, and oncologists currently have no targeted treatments to offer them. Saha is tackling ICC from every angle, working to improve detection, create better therapies, and even, perhaps, help people take steps to avoid developing ICC in the first place.

He chose to focus on gastrointestinal malignancies — and ICC in particular — because he wanted to make a big difference in patients’ lives.

“As a fellow in medical oncology, I had the option to focus on any disease type,” recalled Saha, who balances treating ICC patients with investigating their disease. “When I was looking around I noticed that there was a lot of progress being made in many of the tumor types … One exception to that was in gastrointestinal malignancies.”

An encounter with a single patient cemented Saha’s decision to study ICC specifically. The patient was just 23 years old and already had metastatic disease. As part of a large research project, the genome of the patient’s tumor was sequenced.

“This patient was one of first patients identified with IDH-mutant cholangiocarcinoma,” said Saha, noting a key molecular subtype of ICC.

IDH stands for isocitrate dehydrogenase, a protein that plays a critical role in processing energy within our cells. Mutations in the IDH gene produce a rogue IDH protein that upends normal cellular metabolism. It’s now known, thanks in part to Saha’s research, that altered IDH predisposes certain liver cells to develop into cancer. But at the time, the patient’s IDH mutation was merely scientifically interesting — oncologists didn’t know what the implications of such a finding might be for the patient’s treatment.

“That made me realize we had zero understanding what the IDH mutation was doing,” Saha said. “So I could tell the patient, ‘You have this mutation, but I have no idea what it means.’ … I wanted to change that.”

He already knew firsthand how a good doctor could change patients’ lives for the better. His mother was a psychiatrist in a tiny town in South Carolina. Saha often worked at her clinic and remembers his mother’s patients thanking her when they saw her around town.

“I could see how dramatic an effect she had on [her patients’] lives,” he said. “I got to see people go from completely out of society to being able to re-enter society with a simple medical intervention.”

It’s his goal to someday similarly help patients with ICC by offering them tailored, life-prolonging therapies. Saha has developed a suite of laboratory models to begin answering the most pressing questions about ICC: What triggers it? How does it progress in early stages? What molecular pathways do ICC cells rely on to survive and grow, and can those pathways be targeted with specific therapies? What distinguishes patients whose ICC responds to treatment from those whose tumors develop drug resistance?

The fact that ICC patients have so few treatment options only motivates Saha to work harder in the lab.

“Seeing cancer patients has been very rewarding,” Saha said, “even if we can’t necessarily offer them a cure or prolong their life for as long as we’d like. We can still have a significant impact on their lives. We can help them to understand their diagnosis and come to the treatment plan that is best for them. And find hope.”

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