Pancreatic Cancer Update - Q1 2016

 

The Quest to Diagnose Pancreatic Cancer Early

Pancreatic Cancer Cell
Pancreatic Cancer Cell

Led by an inter-disciplinary team of scientists and clinicians, the U-M Pancreatic Cancer Center holds the promise to significantly change the bleak statistics associated with this disease by revolutionizing pancreatic cancer care. One diagnostic tool they are advancing involves detecting pancreatic cancer cells in the bloodstream before any sign of cancer is obvious through current diagnostic techniques. The successful hunt for these cells would result in a tool for earlier detection, when treatment is more likely to be successful.

Pancreatic cancer’s distinct, more aggressive biology makes it metastasize at much earlier stages than most other cancers. As survival for other deadly cancers improves, pancreatic cancer will likely move from the fourth to the second leading cause of cancer-related death in the United States around 2020. Diane Simeone, M.D., the Lazar J. Greenfield Professor of Surgery and director of the Pancreatic Cancer Center, hopes that better funding and an increase in inter-disciplinary partnerships will improve the odds for patients with pancreatic cancer. If she has her way, a blood test will detect pancreatic cancer early and suggest customized therapies, giving patients a better chance for a cure.

To make early detection workable, you must first find the handful of pancreas cancer cells circulating undetected in the bloodstream. Dr. Simeone’s team is tracking down PanIN3, the most common precursor lesion in pancreatic cancer. Using microfluidic technology developed by team member Sunitha Nagrath, Ph.D., researchers sift through blood. It’s a lot like looking for a needle in a haystack, but the team is finding circulating tumor cells. In the next phases of research, they will learn to concentrate enough cells to understand their biology further, and then develop molecular imaging that is able to identify the location of the cancer.  Read more about this technology here.

“The Holy Grail is two-fold: a blood test to reliably pick up cells in people at high risk, and molecular imaging to find the source so that the microscopic cancer-in-situ can be treated,” says Simeone. “I believe collaborations like ours that cross schools, colleges and disciplines hold the key to finding pancreatic cancer’s Holy Grail.”

Clinical trials are the path forward, so finding more people interested in volunteering is critical. Only about 6% of pancreatic cancer patients enroll in a clinical trial. If enough patients and people who are at risk participate, it will help assure that future patients with this cancer will know they have a high likelihood of survival.

View pancreatic cancer clinical trials currently open at the University of Michigan Comprehensive Cancer Center

Microfluidics and nanotechnology team up to capture circulating cells

Sunitha Nagrath, Ph.D., an assistant professor of chemical engineering at U-M, leads a team combining multiple technologies to seek out elusive pancreatic tumor cells. In 2013 they developed a device which uses both microfluidics and nanotechnology to capture circulating tumor cells from blood samples of pancreatic, breast and lung cancer patients. The device also supports the cells’ growth for further analysis. Microfluidic technology like this for liquid biopsy is revolutionizing what we know about cells at the genetic level and is being used in both basic science and clinical research.

Now, Nagrath and her team are customizing the device at the Pancreatic Cancer Center to look for elusive pancreatic tumor cells.

“Once you detect circulating tumor cells, you can tell a lot about the disease; for example, the kind of cancer, its genetic makeup, how it responds to the environment and therapies, how aggressive the cancer is and so on. For someone with pancreatic cancer, the only way currently to know these things is through studying a biopsy,” she says.

Nagrath believes that devices like the one her team is customizing will someday be able to detect pancreatic cancer early, analyze the cells to determine the best targeted therapy for the patient, and monitor the circulating tumor cells over time to see how they are responding to treatment – all before a solid tumor is big enough to be seen using conventional imaging tests like CT or MRI.

The device uses a specialized microchip to capture cancer cells as blood flows over the chip. The chip knows what to look for because it has been told to target a specific marker. Once the rest of the fluids are washed away, researchers count the remaining cells and extract the genomic information. In the case of pancreatic tumor cells, a recent advance using nanomaterial graphene oxide by Nagrath’s team has made the chip ultra-sensitive, which was necessary in order to capture the elusive pancreatic tumor cells.

“It is a huge challenge to find and measure pancreatic tumor cells. There may be only a dozen or so of these cells circulating with billions of other cells in the blood, and they look and behave a lot like all the other cells. Imagine running a comb through a haystack to look for a needle,” she says.

As work on the microfluidic device continues, it should become sensitive enough to look at a small amount of blood and reliably determine if a patient has – or doesn’t have – circulating pancreatic tumor cells.

Nagrath will label this research a success when she can process 20 milliliters of blood quickly and reliably in a few hours for one patient and learn the number of pancreatic tumor cells, the genetic characteristics of these cells, and how a patient’s disease might respond to a targeted therapy.

“The incredible diversity of clinical and engineering colleagues, which is so strong here at Michigan, is essential to achieving our research goal. This kind of multidisciplinary collaboration is going to change the cancer detection paradigm,” she says.

New clinical trial tests adding Wee1 inhibitor to pancreatic cancer treatment

A Phase 1 study now open at the U-M Cancer Center is adding the Wee1 inhibitor MK-1775 to standard gemcitabine plus radiation therapy for patients with unresectable pancreatic cancer. This study builds on almost 20 years of research at the University of Michigan focused on improving the treatment of unresectable pancreatic cancer.

The study, which is the first to test this combination of MK-1775 with radiation and gemcitabine in patients with pancreatic cancer, stems from laboratory research led by Ted Lawrence, M.D., Ph.D.  It is based on the finding that normal cells have two ways to protect themselves from DNA damage produced by chemoradiation, but pancreas cancer cells have only one way.

In preclinical studies, inhibiting the Wee1 kinase by MK-1775 cancels out the one remaining protection that cancer cells have, causing only the pancreatic cancer cells to die. Normal cells remained unaffected in this model.

As part of the clinical trial, participants will take MK-1775 orally 3-4 hours after gemcitabine infusion and again 24 hours after gemcitabine infusion during each week of treatment. This is a dose escalation trial to test the maximum tolerated dose of MK-1775. Radiation therapy will be given concurrently with gemcitabine and MK-1775 for five weeks. MK-1775 is given with gemcitabine alone before and after the combination treatment with radiation.

We invite you to contact us if you have a patient who may be eligible to participate in this important study aimed at improving the outcome of treatment for patients with local and systemic pancreatic cancer.

For information about referring your patients to this trial, “A Dose Escalation Trial of the Wee1 Inhibitor MK1775, in Combination with Gemcitabine (+Radiation) for Patients with Unresectable Adenocarcinoma of the Pancreas,” please contact principal investigator Ted Lawrence, M.D., Ph.D., via M-LINE at 800-962-3555.