Advances in Pancreatic Cancer Research: Q&A With Christine Iacobuzio-Donahue, MD, PhD

Pancreatic cancer is one of the deadliest forms of cancer, with just 7 percent of patients living five or more years after diagnosis. This year alone, about 53,000 U.S. adults are expected to be diagnosed with the disease, and nearly 42,000 to die of it. One reason for the poor prognosis is that pancreatic cancer is often diagnosed at an advanced stage, making it more difficult to treat.

This week, scientists from around the world will convene in Orlando, Florida, as the AACR hosts a conference titled Pancreatic Cancer: Advances in Science and Clinical Care. The conference will include discussion on the biological mechanisms of pancreatic cancer, drug development, epidemiology and risk factors, patient perspectives, and more. Lead sponsors of the conference are The Lustgarten Foundation, which works to advance scientific and medical research on pancreatic cancer, and the Pancreatic Cancer Action Network, which advocates for research and provides patient support.

We spoke with conference co-chairperson Christine Iacobuzio-Donahue, MD, PhD, director of the Medical Donation Program and associate director of cancer genomics in the David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York, about some of the programming on tap for the meeting.

A study published in the AACR journal Cancer Research in 2014 projected that pancreatic cancer would become the second leading cause of cancer deaths by 2030. Does that still seem to be a realistic prediction, and how does that inform and influence the work researchers are presenting at this meeting? 

Time will tell if it will actually turn out that way. It is only a prediction, but a very important one. It is possible that once we pass the baby-boomer effect, incidence and death rates may actually fall. However, those projections have been very important for raising awareness of this disease. Increased awareness can result in a greater sense of urgency to find a cure for pancreatic cancer, which is a good thing.

Histopathogic image of pancreatic adenocarcinoma arising in the pancreas head region. Source: Wikimedia Commons.

What novel approaches to researching and treating pancreatic cancer will you be discussing at this year’s meeting?

I will be discussing the mechanisms of treatment resistance identified by whole-exome sequencing of primary and metastatic pancreatic cancer tissues obtained from courageous patients who volunteered to undergo an autopsy after they died.

My co-chair Manuel Hidalgo, MD, PhD, of Beth Israel Deaconess Medical Center in Boston will discuss issues and novel developments in preclinical drug development using patient-derived xenograft models.

What session are you most looking forward to attending? Why?

The final wrap-up session will feature a panel discussion moderated by my co-chair, Robert Vonderheide, MD, DPhil, from the Abramson Cancer Center at the University of Pennsylvania. The wrap-up session will focus on the big picture as we move forward with pancreatic cancer research. I expect it will be lively and informative.

What areas of basic pancreatic cancer research are currently yielding the most exciting progress?

Targeting the DNA double-strand break repair pathway seems to be the most promising avenue towards increasing survival right now.

You have a plenary session devoted entirely to immunotherapy and pancreatic cancer. Does pancreatic cancer involve any unique challenges or barriers to immunotherapeutic treatment?

Biologically, a barrier is that pancreatic cancer does not have a high mutational burden for immune checkpoint therapy to be broadly useful as it is in other tumor types. There also appears to be many mechanisms of immuno-evasion in pancreatic cancer.

These barriers are not insurmountable with dedicated research, but they do make the potential use of immunotherapy more complex than for tumors such as melanoma, for example.

You have some researchers planning to discuss possibilities of earlier detection. How close are we to that possibility, and how would it improve the prognosis for most patients?

Human tumor cells from the pancreas stained with an immunocytochemical stain with methyl green in the background and magnified to 400x. Source: Dr. Lance Liotta Laboratory, NCI.

There is still work to do. The most realistic possibility is identifying patients with germline risk variants who do not have a history of pancreatic cancer, as they have the greatest potential for intervention to prevent the disease. Liquid biopsies are more challenging in pancreatic cancer than other tumor types because the overall amount of circulating tumor DNA is much lower. Screening will not improve prognosis for patients already diagnosed with the disease, but can lower mortality rates by detecting curable lesions early.

What are some aspects of pancreatic cancer research that you think will be particularly interesting in the coming year?

Defining the genetic basis of recurrent pancreatic cancer will prove to be paradigm-changing in our understanding of this disease. To provide a basis for this problem, only 10 to 15 percent of patients with pancreatic ductal adenocarcinoma (PDA, the most common form of the disease) are eligible for a potentially curative resection. Of those, the vast majority will develop recurrent PDA in the pancreas, the abdomen, or in distant sites. To date, this has not been studied, largely because the resources have not been available. Therefore, the information we’re now gathering from research autopsy participants is quite valuable. The extent that this knowledge will change treatment remains to be determined, but it is sure to change our thinking of the complexity we are facing.

I understand that the Pancreatic Cancer Action Network will be holding a meeting just prior to the start of the conference, and some advocates are planning to stay on and attend the conference. How do you foresee researchers and advocates working together to improve patient outcomes?

Advocates play an important role by keeping researchers focused on the questions that really matter, rather than drifting into interesting questions that will not change treatment paradigms.

Christine Iacobuzio-Donahue, MD, PhD

Christine Iacobuzio-Donahue, MD, PhD, is director of the Medical Donation Program and associate director of Cancer Genomics for the David M. Rubenstein Center for Pancreatic Cancer Research at Memorial Sloan Kettering Cancer Center in New York.

Resources on pancreatic cancer:

The conference will mark the debut of Let’s Win, a new online community supported by The Lustgarten Foundation in partnership with the Pancreatic Cancer Action Network and others. The site, conceived by pancreatic cancer patient Anne Glauber and her doctor, Allyson Ocean, MD, provides information on innovative, science-driven treatments for pancreatic cancer with the ultimate goal of extending and enhancing lives.

The editors of the AACR have curated a selection of impactful journal articles on pancreatic cancer from AACR publications. The collection is freely available here. For more information on the AACR Foundation’s support of pancreatic cancer research, see our website.