Targeted Therapy for Pancreatic Cancer

Pancreatic cancer is a disease that far too often remains difficult to treat successfully.

Through research that has found more effective chemotherapy regimens for pancreatic cancer, coupled with a better understanding of pancreatic cancer tumor biology, another treatment called targeted therapy has gained significant traction among scientists and clinicians.

“We have so much excitement in the field right now because there are new approaches and new drugs being tested in so many different trials,” says Dr. Margaret Tempero, Director, University of California San Francisco Pancreas Center and Leader, Pancreas Cancer Program. “However, nothing about pancreatic cancer is simple, but I do think that what we have learned about tumor biology is providing us with important information for new approaches to treatment, such as targeted immunotherapy.”

One targeted drug now under investigation in pancreatic cancer is called ibrutinib, which is already being used to treat chronic lymphocytic leukemia, mantle cell lymphoma, and a rare form of cancer called Waldenstrom’s macroglobulinemia.

How Targeted Therapy Works

Unlike traditional chemotherapy, which works by killing cells that multiply quickly, whether normal or cancerous, targeted therapy is more precise. It works by stopping or slowing the growth or spread of cancer at the cellular level. Very simply, cancer cells need specific molecules, such as proteins, to survive, multiply and spread. These molecules are usually made by the genes that cause cancer, as well as the cells themselves.

In a targeted approach to treatment, therapies are designed to interfere with, or specifically target, these molecules or the cancer-causing genes that create them. In some cases, the drug will attach to the molecule it targets, stopping it from doing its job. Other times, the drug will physically block the molecule from the place it normally goes. By stopping the normal work of these molecules, cancer’s growth can be slowed or even stopped.

Testing a New Targeted Drug

One type of immune system cell is called a B cell. Research shows that B cells help create an environment in which pancreatic cancer can develop and grow. But ibrutinib blocks Bruton’s tyrosine kinase, a vital component of B cell receptor signaling. In doing so, it disrupts a number of molecular signaling networks in the immune environment and “reprograms” the immune profile surrounding the cancer. In animal models, this results in more effective tumor control.

Data presented at the 2017 American Association for Cancer Research (AACR) Annual Meeting suggest that ibrutinib may be an effective therapeutic option for pancreatic cancer as shown in pre-clinical studies. The study evaluated the use of ibrutinib in two different preclinical transgenic mouse models of pancreatic cancer and found treatment with ibrutinib not only dramatically reduced tumor cell proliferation and inflammatory cell infiltration, but also was associated with reductions in collagen deposition in the stroma. The mice treated with ibrutinib also experienced longer survival, particularly when the therapy was used in combination with gemcitabine.

Now, in early trials, researchers are looking at its effects in humans. “Patients are very interested in this and are very eager to try new things,” says Dr. Tempero, who leads the UCSF portion of the national “dream team” on pancreatic cancer, a project designed to accelerate treatment and discoveries for pancreatic cancer. “Patients know how devastating this disease can be, and many not only want to move the science forward to help themselves, but also other people in the future.”

Dr. Tempero is actively involved in a global, multi-institutional study with over 400 patients. The study will look at ibrutinib vs. placebo in combination with nab-paclitaxel and gemcitabine for first-line treatment of patients with metastatic disease. The study is ongoing and has completed enrollment. The fact that this trial recruited patients ahead of schedule shows just how interested patients are in trying these new approaches, said Dr. Tempero, who is leading a smaller, similar trial at UCSF.

Hopefully this trial will demonstrate improved survival with ibrutinib and if it does, it will likely lead to FDA approval of ibrutinib for pancreatic cancer therapy, Dr. Tempero concludes.  “We need to make breakthroughs for our patients,” she said. “They deserve our best and our continued work. We can always offer hope, but we need to find better treatments.”

Learn more about ibrutinib by reading “Testing Targeted Immunotherapy Against Pancreatic Cancer.”