April 15, 2024

Elana Simon was 10 years old when she started experiencing severe pains in her abdomen. For two years, confused doctors suggested diagnoses including lactose intolerance, Crohn’s disease and stress. It was not until 2008 that they pointed out the real cause. Elana suffered from fibrolamellar carcinoma (FLC), a rare, usually fatal form of liver cancer.

“In a way it was comforting to have a word for what was wrong with me after so much confusion about my condition,” Elana told the Observer. “Pre-diagnosis, my life was a mixture of discomfort and fear. Now I had something to focus on.”

Surgeons were able to cut out the tumor, which was still spreading from her liver, and Elana survived. Indeed, she triumphed over her adversity in a remarkable manner. After studying at Harvard, she joined the lab at New York’s Rockefeller University run by her father, Prof Sanford Simon, who has devoted his career to tackling FLC since his daughter’s diagnosis.

“The moment I learned about Elana’s condition is etched in my memory,” Prof Simon told the Observer. “I was determined to find out what was causing it and find ways to counter it.

“I was working as a cell biologist at the time and could have traveled throughout the rest of my career. Elana’s diagnosis changed everything and I completely changed the direction of my research, which is now completely focused on the cancer.”

Research at Prof Simon’s laboratory has since led to several major breakthroughs in establishing the cause and behavior of FLC. Now that work has been further boosted by a £20m grant from Cancer Research UK, given this month as part of its Cancer Grand Challenges awards. The awards are awarded – in partnership with the National Cancer Institute in the USA – to research groups whose new ideas offer the greatest potential to advance cancer research.

A consortium including Prof Simon’s laboratory has received its Cancer Grand Challenge grant to help it develop new, easily accessible treatments for conditions such as FLC. Currently, treatments for solid tumors in children still rely on decades-old chemotherapy regimens, and the goal of the program is to develop new, less complicated interventions.

Their victory speaks volumes for the success scientists have had with FLC in recent years. When Prof Simon decided to start studying the cancer, its cause and roots were still a puzzle. Was it a single disease or were cases comprised of people with different conditions who all had similar symptoms.

In addition, the cause of the disease was a mystery. “We didn’t know if it was inherited, or caused by a specific environmental insult,” he said.

That’s when Elana – then a high school student but now studying for a PhD in computer science and cancer biology at Stanford University in California – stepped in. “I ended up making a lot of friends who were about my age and who had gone through various pediatric cancer diagnoses and treatments,” she said. Elana and one of these friends launched a YouTube appeal for other people with that cancer to submit tissue samples to her father’s lab. They ended up with 15 samples in total, and these played a crucial role in helping the team at Rockefeller make key discoveries about the disease.

“First, we found that it was a single disease with one mutation that was the same for every tumor sample. It caused the disease,” said Elana, who pioneered this part of the project.

In addition, the team found that FLC was not an inherited condition. “It’s caused by a single environmental insult, and that was crucial,” Prof Simon added, “because it suggested that if you cut out a tumor before it’s spread, it means you can stop the disease. It was unlikely to happen again.”

Fibrolamellar carcinoma was very rare, Prof Simon admitted. Some studies suggest that there are only a few hundred cases worldwide each year, although more recent analyzes suggest that the figure may reach thousands.

“The crucial point is that when you look at common cancers in adults, you come across all sorts of background genetic mutations in cells, and that makes it difficult to determine what’s driving the disease,” he said. “With a childhood cancer like FLC, however, relatively few mutations develop and therefore it becomes much easier to understand what is going on. In this way, cancers like these provide critical insights that reveal general principles.”

Another cancer it applied to was the rare retinoblastoma eye tumor, Prof Simon said. Studies of patients with the condition have revealed the existence of tumor suppressor genes: these usually limit the spread of cancer cells, but sometimes fail. Therapies based on this discovery are now being developed for many cancers.

“That’s what we hope we can do with the work we’re doing on this carcinoma,” said Elana. “It will not only help people like me who get FLC, but will give general insights about other cancers. The Cancer Grand Challenge funds will make a huge difference to those efforts.”

At the same time, it is hoped that easily administered therapies for FLC will be developed from the insights already gained about the disease.

“Ultimately, we want to create drugs that can be administered as pills in places where the health provision is poor,” Prof Simon said. “That’s the ultimate goal.”

Source link

Leave a Reply

Your email address will not be published. Required fields are marked *