LEBANON — There are cancers, and there are worse cancers. Then there is pancreatic cancer.
This year 60,000 people will be diagnosed with pancreatic cancer, according to the American Cancer Society, and 48,000 will die from the disease, an 80% mortality rate. The five-year survival rate is less than 11%.
And having just displaced breast cancer as the third-ranked cause of cancer deaths, pancreatic cancer is projected to become the second-leading cause of cancer deaths by 2030 in the U.S., behind lung cancer.
“It’s one of the most difficult cancers to cure,” said Dr. Steven Leach, director of the Norris Cotton Cancer Center at Dartmouth-Hitchcock, explaining that he was led to study the disease when as a young doctor he witnessed firsthand its devastating course.
“I started my career as surgical oncologist and I saw pancreatic cancer patients facing their disease with tremendous courage,” Leach said, recalling how patients dealt with what is, in effect, a death sentence.
Now Leach and his research partner, cancer biologist Surajit Dhara, have formed a company, Episteme Prognostics — Dhara is the president and Leach is chair of the Scientific Advisory Board — to commercialize a precision approach they have developed in the lab to tackle pancreatic cancer that could guide the best course of therapy for a patient, they said.
The pancreas helps with digestion, regulates blood sugar and lies in the abdomen deep inside the body. Treatment of pancreatic cancer presents many obstacles, not least because there is no method yet for early detection of a tumor on the pancreas, like there is with mammograms for breast cancer or pap smears for cervical cancer.
So by the time a tumor makes itself known to warrant a test, the cancer has already irreversibly progressed in the vast majority of cases.
Moreover, traditional treatments, such as surgery to remove the tumor, tend not to be of much help with pancreatic cancer. Half of all patients who have had a pancreatic tumor removed relapse within a year despite chemotherapy. Odds of long-term survival for most of the remaining group diminish quickly.
“There’s something about the intrinsic biology of the disease that makes it so resistant” to treatment, Leach said.
Leach, 61, joined Norris Cotton in 2017 after previously heading a pancreatic research center at Memorial Sloan Kettering Cancer Center in New York. Dhara, 50, grew up and was educated in India, where he earned a Ph.D. in cell biology before coming to the U.S. on a post-doc at Johns Hopkins University in 2003.
It was at Johns Hopkins, in fact, where Leach’s and Dhara’s paths first crossed. But they didn’t begin collaborating until they teamed up on pancreatic cancer research at Sloan Kettering. When Leach was tapped to head Norris Cotton, he recruited Dhara as the first member of his lab team and tasked him with setting it up.
Today, Leach Laboratory, based at the Williamson Translational Research Building on the Dartmouth-Hitchcock Medical Center campus in Lebanon where Dhara is the senior researcher, has nine members.
University-affiliated biotech startups, despite the billions in government funding and private investor money funneling into them, are a notorious long shot; one recent study in the academic journal Nature Biotechnologyfound that fully 47% of them qualify as a “likely or definite” failure, 30% are still a “work in progress” and at most only 23% could be judged a success.
Nonetheless, Episteme Prognostics — “episteme” is an English transliteration of an Ancient Greek word that means “knowledge” or “skill” — already has a head start.
The 18-month-old company is seeking to commercialize a technology, the invention of which has been largely funded by the National Institutes of Health and based on research in collaboration with multiple institutions. The goal is to provide a low-cost way to determine whether a patient with a cancerous pancreatic tumor will respond to traditional chemotherapy or whether the patient is a better candidate for alternate treatment.
(The current inability to distinguish between the two groups of patients results in a trial-and-error process that delays prognosis and therefore puts the patient at higher risk while the disease progresses.)
The novel test, which would be packaged as a diagnostic kit, allows “the patient to know within a week of diagnosis if they are going to respond to chemotherapy, which is a big blessing for an oncologist designing a therapy” regimen, Dhara said.
There are 500,000 cases of pancreatic cancer diagnosed globally each year — most hospitals have their own test lab, making the potential market for the kits significant.
But the vast majority — 90% — of pancreatic cancer patients do not respond to chemotherapy, making it incumbent to find a better way to battle the disease. And that’s where the next phase of Leach and Dhara’s research kicks in.
To develop a therapy regimen, the Norris Cotton researchers are focusing on an epigenetic approach that works at the gene level rather than the cellular level. Epigenetic therapy seeks to “reprogram” the genes in chemo-resistant tumors to make them more responsive to chemotherapy treatment.
In other words, rather than focus on developing a therapy regimen that combats the cancer cells directly — a long-standing approach in battling cancer — Leach and Dhara are looking to make tumors more receptive to most effective treatment.
“Chemotherapy has been around for 50 or 60 years,” Dhara said. “It’s the gold standard.”
Ultimately, if Leach and Dhara’s theory and research holds up, it could lead to as epigenetic-developed drug that would be administered either orally or by injection, and lead to better outcomes and quality of life for patients.
Such a happy outcome, if it turns out to be the case, is a ways off, however. The researchers hope to begin clinical trials this summer.
In the meantime, Dhara, in his role as president of Episteme Prognostics, is meeting with investors for seed funding, where the first round for startups typically runs in the low-single-digit millions. Commercialization would likely require a second round, generally a multiple of the first round.
Because Leach heads Norris Cotton, he is prohibited from holding a financial stake in Episteme to avoid potential conflicts of interest.
That means Dhara is working more closely with potential investors, though his area of expertise is the research laboratory, not the board room. He’s learning, he said.
“This is my first venture,” Dhara said. “But Dartmouth is training me very well.”
Contact John Lippman at jlippman@vnews.com.