When it comes to pancreatic cancer research, it’s tough to pin surgeon and scientist Dr. Diane Simeone* down to just one topic.
That’s because she is involved in research to not only better understand the molecular basis of a disease that has proven resistant to many therapies, but to also quickly bring laboratory findings to patient care. This translational approach has proven to be her life’s work.
“I see patients nearly every day, many of whom are not surgical candidates and even if they are, we all know the long-term prognosis is not good for the majority of patients who undergo surgery,” says Simeone, the Lazar J. Greenfield Endowed Professor of Surgery and Physiology at the University of Michigan Medical Center. She is also founding director of the University of Michigan’s Pancreatic Cancer Center.*
“We simply need to do a better job coordinating research, making research applicable to patients, and continue to explore scientific endeavors that can make a difference for our patients,” she adds.
Science Geared Toward Patient Care
In 2007, Simeone’s lab was the first to identify pancreatic cancer stem cells, the cells in a tumor that spark tumor growth and spread. Current cancer treatments sometimes fail because they are not attacking the cancer stem cells, she says. Her ongoing research is geared toward deeply understanding cancer stem cells so that targeted drugs could be developed to kill them.
The team has already been able to identify drugs that target these cancer stem cells by blocking critical signaling pathways that plays a role in how these cancer stem cells function. And clinical trials are ongoing to see just how well these drugs may work.
“It is very exciting that this work is moving into clinical trials, but we may need to tackle pancreatic cancers from more than one angle,” says Simeone, adding that in these cancers, stem cells often only make up a small percentage of the cells found in a pancreatic tumor. “The real issue was and still is the fact that the majority of the cells of a tumor are aggressive and very resistant to treatments.”
Her team may have found the reason why pancreatic cancer is so aggressive: a gene they discovered called ATDC which drives the formation of cancer stem cells in patient tumors. The technical name for the gene is Ataxia Telangiectasia Group D Complementing gene. Its expression (basically, how it is “turned on”) is about 20 times higher in pancreatic cancer cells compared to healthy, normal cells. It’s also highly expressed right at the point when pre-cancerous cells become malignant.
“This gene is what fuels the fast growth of cancer cells. It makes them aggressive and treatment resistant because it promotes the formation of cancer stem cells early on,” notes Simeone. “Targeted drugs could potentially make the cells more responsive to treatments that are already available to patients.”
Replicating A Patient’s Tumor
Simeone imagines a time in which a single sample of blood from a pancreatic cancer patient could provide enough information to personalize treatment to eradicate the disease.
Her research team has already developed a technique to isolate circulating tumor cells—cells of a tumor that break off and enter a person’s bloodstream— and is working with pancreatic cancer experts globally to find the most efficient ways to assemble the cells into a microtumor to be studied in 3-D in the laboratory. The goal: rapid testing of drug combinations, personalized to that patient.
“Today, doctors who treat pancreatic cancer patients simply make an assumption of what kinds of cells are in a tumor, and the goal is just to shrink the tumor,” Simeone explains. “But we do know that some of the cells in a tumor are more lethal, more aggressive, than others.
“Isolating a patient’s own cancer cells from a simple blood sample and tailoring treatment has the potential to be a huge step forward, a game changer for treatment.”
Making Clinical Trials Relevant to Pancreatic Cancer Patients
Simeone wears two hats: clinical scientist and a surgeon. And it is difficult—as it is for any medical professional—to tell patients medicine and science has nothing more to offer. “We have made progress, but we need to make so much more to make research findings relevant to patients,” she says. “One way to do that is to get more cooperation around clinical trials.”
That’s why Simeone is so excited about her role in a new initiative called Precision Promise, a bold effort by the advocacy group Pancreatic Cancer Action Network to provide personalized, molecularly driven, evidence-based treatments for every pancreatic cancer patient. It’s a lofty goal, but one that she believes is possible and absolutely necessary. Simeone serves as the U.S. lead on the Precision Promise effort.
“What we want to do is have trials designed specifically for patients,” says Simeone, noting that clinical trials traditionally are designed to find patients to fit eligibility requirements that are dictated by a trial design. This proposed new approach puts patients at the center of trial design and, hopefully, will more appropriately reflect the needs of patients.
“Pancreatic cancer survival is often measured in months, not the years it takes to complete trials, many of which have been poorly designed,” she explains. “The kind of cooperative model proposed by Precision Promise allows us to be more nimble and have real collaboration among researchers, drug manufacturers, doctors who are on the front lines treating patients and, most important, the patients and families affected by this disease.”
Her hope is to increase clinical trial enrollment for pancreatic cancer, which has been low compared to other solid tumors. “Pancreatic cancer is projected to move from the fourth to the second leading cause of cancer-related death in the U.S. by about 2020. It is so evident that we need to do something right now to make a difference as quickly as we can.”
Simeone has one profound hope. “As a clinician and scientist I am always going to be asking questions and a lot of my work is in the lab, but I am a doctor who also sees patients. And what I want to do is be able to tell these patients science is finding answers and leading to changes in patient survival – we cannot be satisfied until we reach that goal.”