Pancreatic cancer is one of the deadliest and most aggressive cancers and is projected to surpass breast, prostate, and colorectal cancers to become the second leading cause of cancer-related deaths. Even if initially responsive to chemotherapy, pancreatic cancer almost inevitably becomes resistant to treatment.
Now a researcher at The University of Texas MD Anderson Cancer Center hopes to deprive pancreatic cancer of the cellular building blocks it relies on to supply its out-of-control growth. This may eventually lead to therapy that could demolish pancreatic cancer.
Cancer biologist Pawel Mazur was recruited from Stanford University, where he was a postdoctoral fellow, with the help of a First-Time Tenure-Track Award from CPRIT in 2016. He joined the Department of Experimental Radiation Oncology.
Pancreatic cancer, like most cancers, is driven by a key mutation initiates its development and sustains its out-of-control growth. Targeting that mutation with chemotherapy hasn’t improved the survival rate for the disease, which hovers around five percent after five years. By the time pancreatic cancer causes enough symptoms to be diagnosed, patients are usually already suffering from metastatic disease, and most die within a year of diagnosis.
Mazur is interested in studying and potentially targeting other cellular machinery involved in cancer. After all, he says, while an oncogene mutation may cause the cancer cells to grow out of control, there are many other enzymes that are involved in actually building the new cells — the engineers, if you will.
In particular, he’s found an enzyme that enables cells to utilize protein to build themselves up. The cancer steals protein from other parts of the body, causing pancreatic cancer patients to quickly lose much of their muscle mass.
All cells throughout the human body use protein synthesis, so it’s not generally a good target for chemotherapy. But Mazur discovered that this particular enzyme is only activated during tissue regeneration or periods of rapid growth, like early childhood. Pancreatic cancer amplifies this enzyme many hundreds of times over the amount found in normal cells.
Interfering with this enzyme could potentially starve cancer cells of the resources they need for rampant growth and make it possible to kill them with other forms of chemo- or immune therapy.
Mazur’s laboratory contains many different types of resources, so a company that is developing a drug candidate will utilize his lab to test any potential therapies. Anything the company develops and finds to be effective in the laboratory will be tested in a clinical trial, initially in lung cancer patients, because they typically live longer than pancreatic cancer patients and there are 20 times as many cases every year. But if a drug candidate succeeds, it will be tested against pancreatic cancer.
“The most important point is that this may be a universal mechanism,” Mazur says. “I wouldn’t be surprised if many tumors, if not all, utilize this method of self-renewal and build-up. The amount of the enzyme correlates with the aggressiveness of the cancer.”
CPRIT’s kick-starter investment in Mazur’s work has already yielded $10 million in follow-on funding from the National Institutes of Health. He’s building on his success to study other enzymes that may allow immune therapy, currently highly effective in blood cancers, to be used to treat pancreatic and other solid tumors.
Mazur received his undergraduate and master’s degrees in molecular biology from Warsaw University, Poland, and his Ph.D. in molecular biology and cancer research from the Max Planck Institute of Biochemistry and Technical University of Munich, Germany. He joined Stanford University as a postdoctoral fellow in genetics and pediatrics in 2011.
Read Less
