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Dr. George Miller receives his Innovative Grant alongside Pancreatic Cancer Action Network President and CEO Julie Fleshman and AACR 2014 President Dr. Charles Sawyers.
©2014/AACR/Todd Buchanan
Among the ways that healthy cells avoid becoming transformed into cancer is through a process called apoptosis, or programmed cell suicide. If cells accumulate damage through an infection, injury or a mistake incorporated into their DNA code, the damaged cells undergo apoptosis (induce their own death) through a highly regulated process that ensures that the damage does not spread or cause any problems to the person’s tissues, organs or entire body.
Many of the proteins that control apoptosis are considered tumor suppressors, meaning that they function to prevent cellular changes that can induce cancer formation.
But New York University associate professor of surgery and cell biology, and recipient of the 2014 Pancreatic Cancer Action Network – Celgene Corporation Innovative Grant, George Miller, MD, describes a new mode of pancreatic cancer cell death, called necroptosis, that may play an important role in cancer cells’ survival and avoidance of an immune response.
Dr. Miller’s most recent findings were published online in the highly regarded journal, Nature, in April 2016.
“We found that besides dying by apoptosis, pancreatic cancer cells also die by necroptosis, and chemotherapies such as gemcitabine increase the rate of necroptotic cell death,” Dr. Miller explained.
Like apoptosis, necroptosis is a highly regulated mode of cell death.
“Not surprisingly, if you block the cells’ ability to die via necroptosis, pancreatic cancer cells in a dish will grow even faster,” said Dr. Miller.
“But we were surprised to learn that disrupting necroptosis in mice with pancreatic cancer led to their tumors progressing more slowly.”
This unexpected finding was attributed to necroptosis-derived proteins promoting the suppression of immune responses against pancreatic cancer. When the necroptosis was blocked, the pancreatic tumor became more vulnerable to an anti-tumor immune attack.
Being able to block pancreatic cancer cells’ ability to hide from the immune system is a key component of immunotherapy approaches.
Although the work is preliminary and so far has been evaluated in mice and not humans, Dr. Miller and his team’s data suggest that blocking the activity of proteins involved in necroptosis could hold therapeutic promise in pancreatic cancer.
He also commented that this work would not have been possible without his 2014 Innovative Grant from the Pancreatic Cancer Action Network, generously funded by Celgene Corporation.
He said: “Equally important to the financial resources provided by the Pancreatic Cancer Action Network was the opportunity to be part of this inspirational community.”
