Adenocarcinoma of the pancreas is the fourth leading cause of cancer death in men and women in the United States. This year, about 46,000 people in this country will be diagnosed with pancreatic cancer, and more than 39,000 will die of the disease. The ASCO Post recently spoke with Margaret A. Tempero, MD, Director of the University of California, San Francisco (UCSF) Pancreas Center, whose research career has focused on pancreatic cancer, especially in the area of investigational therapeutics. Dr. Tempero shed light on the current state of pancreatic cancer therapy and research.

Major Advances

What have been the biggest advances in pancreatic cancer seen during your career?

The recent introduction of some reasonably effective combination chemotherapies is an important advance. Considering where we were a decade ago, having the opportunity to treat patients now and see them go into remission and then be able to take them off treatment for observation is nothing short of miraculous. Now that we have disease-stabilizing chemotherapy, it will allow us to go to the next level, where we’ll be able to try some of the newer strategies that we’ve only dreamed of trying in pancreatic cancer.

The other major advance, which has accelerated our ability to understand the biology of this disease, has been the introduction of cutting-edge genetically engineered mouse models, a technology that has evolved over the past 10 years or so. These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer, and they will have a huge impact on our approach to developing new therapies as we move forward.

Early Detection

Early detection in pancreatic cancer is very uncommon. Is this something we have to accept, or are there any markers forthcoming that may show promise?

The disease is somewhat diverse in its biology, and there are patients who seem to have a very early propensity for metastases even with very small primary tumors. Then there are other patients who don’t have a propensity for metastatic involvement and instead have slower-growing locally invasive disease. So in this subset of patients that have localized, slow-growing disease, early detection would have clinical benefit.

We need to come up with a detection marker on the molecular level with a cost-effective, high-throughput assay for patients at average risk and an imaging tool that could be used to screen patients at high risk. That said, risk stratification is something we don’t know how to do very well in this disease, and it remains a very important research area.

Risk Factors

Cigarette smoking is related to pancreatic cancer. Are there other lifestyle drivers of this disease that we know about?

Cigarette smoking is a risk factor in pancreatic cancer but not nearly at the ratio we see in lung cancer and head and neck cancer. Obesity is also a risk factor for pancreatic cancer, at about the same ratio as cigarette smoking. These are two environmental risks based on lifestyle that we can modify and thereby ultimately reduce disease incidence. That said, in the overall picture of pancreatic cancer, this impact would be small.

Outside of familial disease, the biggest risk factor is something we don’t want to change, and that is successful aging. Pancreatic cancer, like most cancers, is a disease associated with aging. Since we have an expanded aging population, we are going to see an increase in this disease in patients over the age of 75, so our real challenge is in developing better ways to treat and manage this growing population of older patients.

Newer Approaches

In this era of biologics and the rise of immunotherapy, please discuss how we currently approach this disease and which, if any, of the newer approaches hold promise.

There are several areas that hold promise. For one, studying the microenvironment in this disease and how it influences its biologic behavior is pretty high on our research priority list.

One such strategy is being explored by Halozyme Therapeutics, which has developed a form of hyaluronidase that diminishes the hyaluronan component of the stroma. In doing so, it reduces interstitial pressure and may allow for more effective drug delivery. This approach is already being studied in randomized phase II trials.

The other area of the microenvironment that is being tackled by our Stand Up To Cancer team [see sidebar] is immunomodulation, which seeks to change the immunoenvironment from a protumor to an antitumor environment. To do this, we’re looking at a variety of strategies. For one, we’ve found a connection between B cells and tumor-promoting myeloid cells, so reprogramming B cells with a Bruton’s tyrosine kinase inhibitor plus chemotherapy is one approach. Also, we are exploring some vaccines in combination with checkpoint inhibitors. In fact, there are some vaccines already in very late-stage development in randomized phase III trials.

The early signals are encouraging, and as I said before, finally having chemotherapy agents that stabilize our patients allows this groundbreaking work to move forward. 

Surgical Setting

Please touch on the current role of surgery in pancreatic cancer.

Obviously, if you have an organ-confined lesion, surgery plays an important role in the treatment of pancreatic cancer. And another benefit of the new chemotherapy regimens is to improve the outcome with surgery. We are seeing more reports now on successful surgery with clean margins following preoperative treatment. We need rigorous trials to help us translate this into better outcomes, but the anecdotal information we have is encouraging.

Editorial Position

Congratulations on being named Editor-in-Chief of the Journal of the National Comprehensive Cancer Network (JNCCN). What does this new opportunity mean to you?

The JNCCN is a powerful tool for disseminating the latest information that clinicians can readily translate into their patient care. As someone who has devoted a career largely to one disease site, being the Editor-in-Chief of this journal that so carefully covers malignancies is a real honor. It is also a great way for me to keep up to speed with progress in cancer care.

Closing Thoughts

Please share some last thoughts on this disease, which you have dedicated so much of your career to.

I’ve been involved in treating patients with pancreatic cancer for over 30 years. Frankly, a lot of people thought I was nuts to devote my career to this dreadful disease. But what I learned early on from my mentors was to focus and never let go of my goal. And I’ve come to look at this very vulnerable patient population as my professional mission in life. When I think about how this disease affects my patients, it just makes me want to work harder and harder.

I also feel fortunate to direct the Pancreas Center at UCSF, a very prestigious university with teams of incredible scientists, all of whom are dedicated to the mission of curing pancreatic cancer or turning it into a manageable chronic disease. ■

Disclosure: Dr. Tempero reported no potential conflicts of interest.