Valley News – Dartmouth researchers’ company aims to improve pancreatic cancer testing, treatment – About Your Online Magazine


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, a mortality rate of 80%. The five-year survival rate is less than 11%.

And having just replaced breast cancer as the third leading cause of cancer deaths, pancreatic cancer is expected to become the second leading cause of cancer deaths by 2030 in the US, behind lung cancer.

“It’s one of the hardest cancers to cure,” said Dr. Steven Leach, director of the Norris Cotton Cancer Center in 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 a surgical oncologist and saw pancreatic cancer patients facing their disease with tremendous courage,” said Leach, recalling how patients handled 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 president and Leach is president of the Scientific Advisory Board – to commercialize a precision approach they developed in the lab to fight cancer of pancreas that could guide the best course of therapy for a patient, they said.

The pancreas aids in digestion, regulates blood sugar and sits in the abdomen, deep in the body. The treatment of pancreatic cancer presents many obstacles, not least because there is still no method for the early detection of a tumor in the pancreas, as happens with a mammogram for breast cancer or a Pap smear for cervical cancer.

Therefore, by the time a tumor becomes known to warrant testing, the cancer has progressed irreversibly in the vast majority of cases.

Also, traditional treatments, such as surgery to remove the tumor, tend not to be of much help in pancreatic cancer. Half of all patients who have had a pancreatic tumor removed relapse within a year despite chemotherapy. The chances of long-term survival for most of the remaining group decline rapidly.

“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 doctorate. in cell biology before coming to the US as a postdoctoral fellow at Johns Hopkins University in 2003.

It was at Johns Hopkins, in fact, where the paths of Leach and Dhara first crossed. But they didn’t start collaborating until they teamed up on pancreatic cancer research at Sloan Kettering. When Leach was chosen to head Norris Cotton, he recruited Dhara as the first member of his lab team and charged him with setting it up.

Today, the 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 billions in government funding and the money from private investors funneling into them, are a notorious hit; a recent study in the academic journal Nature Biotechnologyfound that 47% of them qualify as a “probable or definite” failure, 30% are still “work in progress” and at most only 23% can be considered a success.

However, Episteme Prognostics – “episteme” is an English transliteration of an ancient Greek word meaning “knowledge” or “skill” – already has an advantage.

The 18-month-old company is trying to commercialize a technology, the invention of which was largely funded by the National Institutes of Health and based on research in collaboration with several 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 an alternative treatment.

(The current inability to distinguish between the two groups of patients results in a process of trial and error that delays the prognosis and therefore places the patient at greater risk as the disease progresses.)

The new test, which would be packaged as a diagnostic kit, allows “the patient to know within a week of being diagnosed whether they will respond to chemotherapy, which is a huge boon for an oncologist planning therapy,” Dhara said.

There are 500,000 cases of pancreatic cancer diagnosed globally each year – most hospitals have their own testing laboratory, making the potential market for the kits significant.

But the vast majority – 90% – of pancreatic cancer patients do not respond to chemotherapy, which makes it the task of finding a better way to fight the disease. And that’s where the next phase of Leach and Dhara’s research begins.

To develop a therapy regimen, Norris Cotton researchers are focusing on an epigenetic approach that works at the gene level, not the cellular level. Epigenetic therapy seeks to “reprogram” genes in chemo-resistant tumors to make them more responsive to chemotherapy treatment.

In other words, rather than focusing on developing a therapy regimen that fights cancer cells directly — a long-standing approach to fighting cancer — Leach and Dhara are looking to make tumors more amenable to more effective treatment.

“Chemotherapy has been around for 50 or 60 years,” said Dhara. “It’s the gold standard.”

Ultimately, if Leach and Dhara’s theory and research hold up, it could lead to a developed epigenetic drug that would be administered orally or by injection, and lead to better outcomes and quality of life for patients.

Such a happy result, if any, is still a long way off. 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 of startups typically runs in the low-digit millions. Marketing would likely require a second round, usually a multiple of the first round.

As Leach runs Norris Cotton, he is prohibited from holding a financial interest in Episteme to avoid potential conflicts of interest.

This means that Dhara is working more closely with potential investors, although her area of ​​expertise is in the research lab, not the boardroom. He is learning, he said.

“This is my first adventure,” Dhara said. “But Dartmouth is training me really well.”

Contact John Lippman at jlippman@vnews.com.



Paula Fonseca