In January 2006, when Josh Sommer was still an aspiring environmental engineering student at Duke University on winter break, he began experiencing debilitating headaches out of nowhere. Though he felt fine and was an otherwise healthy 18-year-old, an MRI would soon reveal he had a slow-growing tumor pressed against his brainstem and wrapped around several major arteries.
Later that year, Sommer travelled to Pittsburgh to undergo a complicated 10-hour operation to remove the growth. Only after the surgery did his doctor make an official diagnosis: chordoma, a malignant form of bone cancer so rare it occurs in just one out of every one million people.
Chordoma arises when a leftover cell from the notochord, the embryonic precursor to the spinal cord, changes over time and becomes cancerous. Chordomas typically develop at the base of the skull, the lower spine, or the tailbone and often invade the surrounding bone and tissue.
For the 300 people in the United States diagnosed with the disease each year, surgery to remove the chordoma, often in combination with radiation, is the best shot at treating the disease. Unfortunately, the proximity of most chordomas to vital structures in the nervous system makes them difficult to remove without serious, sometimes debilitating, complications.
Making matters worse, removing a chordoma in its entirety—if possible—does not guarantee it will not grow back. “It’s not uncommon for a patient to have five, 10, sometimes 15 surgeries to keep removing the tumor until that’s no longer possible,” said Sommer.
He spent much of his recovery reading as much as he could about the disease, and was devastated to learn that that if his chordoma were to recur, another risky surgery and radiation was his only option.
“There were no drugs approved to treat the disease and, at the time, none in clinical trials either,” he said. With such limited treatment options, most chordoma patients are expected to live an average of seven years after their diagnoses—a statistic he "refused to accept."
By the time Sommer returned to school in the fall, he was determined to do whatever he could to try to change his prognosis. For him, that meant working in the country’s only federally-funded laboratory focused on chordoma—serendipitously located at Duke, in a building Sommer had biked past countless times on his way to class. “I had no experience, but a lot of motivation,” Sommer said.
“From the beginning, he was shooting really high: a cure for chordoma, and he was approaching that in a very rational, tactical way,” said Michael Kelley, an oncologist and associate professor of medicine at Duke, whose lab was leading the effort.
Under Kelley’s mentorship, Sommer joined the lab’s ongoing efforts to identify genes linked to chordoma. Soon after, Sommer was running his own experiments. He began taking fewer engineering classes and more microbiology classes to better understand the disease.
But despite his deepening understanding of chordoma and the progress they were making—Kelley’s lab was pivotal in elucidating the role of a gene called brachyury in the development of chordoma—Sommer was disheartened by the challenges in studying such a rare disease in a research environment in which progress moved at a glacial pace.
“I could see we would only get so far without hitting a wall,” he said.
Money was a major issue. Government agencies tend to fund research that will have the biggest effect across the population, so common cancers—breast cancer, prostate cancer, and so on—usually receive the most funding. Similarly, pharmaceutical companies and biotech firms tend to fund research only if it is likely to be profitable.
Insufficient funding was only one of many challenges. “We didn’t have materials needed to study the disease,” Sommer says. Most chordomas were thrown away after surgery, so tissue samples needed to understand the fundamental biology of the disease were scarce. Cell lines—models of disease made by taking cells from a patient’s tumor and growing it in a plastic dish—were just as hard to come by. Both were needed to understand chordoma at its most basic level and to identify drugs most likely to be effective in patients. “Many researchers’ attempts to study the disease were hamstrung, while others were deterred from undertaking chordoma research projects altogether,” he said.
Perhaps most problematic, though, was the lack of a community and the basic infrastructure to support collaboration. “In science, one discovery informs the next. That was not happening in chordoma.”
Disseminating research findings or sharing research materials, if it happened at all, could take years. So isolated were researchers, adds Kelley, that it was not immediately clear who was working on the disease to begin with. “How can you collaborate when you don’t even know who potential collaborators are?” he said.
Once Sommer realized that the biggest barriers were not necessarily scientific problems, but human ones, he became even more determined to solve them. In 2007, he and his mother co-founded the Chordoma Foundation, where he remains executive director today. To date, the Durham, North Carolina-based foundation has raised almost $5 million to jumpstart research in the disease and encourage widespread collaboration.
One of the first orders of business was building a network of researchers and establishing a conference where researchers worldwide could exchange data. Now a bi-annual event, the conference has helped build a community of more than 200 researchers in labs worldwide.
The foundation also worked to license cell lines from the institutions in which they were created and distribute them freely to chordoma researchers. The availability of such critical research resources made it possible to generate the convincing pre-clinical data that lay the groundwork for clinical trials.
These advances alone, Kelley says, have “created a very active chordoma research community” and “dramatically accelerated the pace of research” in the disease. Forbes magazines agrees; it recently named Sommer to its "30 Under 30" list of innovators who are transforming science and health for the second year in a row.
Having created the necessary infrastructure, the foundation is now supporting research aimed at developing new chordoma treatments. One such project screened more than 2,800 FDA-approved drugs in chordoma cell lines to determine whether any could be repurposed to treat the disease. Another invites researchers or companies to submit investigational drugs to be screened to determine their potential in treating chordoma.
“There might already be drugs out there that are effective in treating chordoma, and we’re determined to find out,” Sommer said. “Otherwise, we’ll have to develop them ourselves, which of course requires a major investment and much more time.” So far, more than 40 drugs screened have shown activity in chordoma; the most promising are now undergoing additional testing.
More recently, the foundation partnered with the National Cancer Institute to expand its ongoing clinical trial of a new treatment called GI-6301, which targets a wayward protein found in most chordomas, as well as in breast, colon, lung, and prostate cancers. The foundation helped complete enrollment in the trial—one of the most time-consuming and costly phases of clinical research—within days of announcing it to the foundation’s active social media community.
“When you’re dealing with a small disease like chordoma, you can’t wait for researchers and companies to come to you,” Sommer said. “We had to make a case that we could help gain eventual FDA approval by efficiently recruiting for a trial.”
This, along with a better understanding of the disease and the resources needed to provide the rationale for clinical testing, has promoted the pharmaceutical and biotech industry to “take an interest in chordoma.”
Indeed, the past few months, Sommer said several companies have approached him about testing their drugs.
In the meantime, the foundation is also directly funding research to better understand the biological underpinnings of the disease. The foundation has already sponsored researchers at the Wellcome Trust Sanger Institute in England to sequence the chordoma genome in its entirety, cataloging more than 400 mutations that provide insight into what biological mechanisms allow the disease to thrive and, more importantly, Sommer notes, “how to most rationally and effectively treat it.”
Sommer’s ultimate goal is to cure chordoma. But, along the way, he hopes to generate knowledge that helps accelerate research for other cancers. “The solutions needed to enable research and treatment development for chordoma are the same for many other rare cancers” Sommer said.
Though he has been cancer-free since his surgery, Sommer must undergo a scan every six months to make sure a recurrence, should there be one, is detected as early as possible. "On most days I’m able to put my own disease out of my head," he said. "But there’s always a what if?"