After discovering that some pancreatic cancer expresses high amounts of intratumoral interferon signaling (IFN), researchers wondered whether they could create a new plan of treatment. According to Medical XPress, researchers from the UCLA Jonsson Comprehensive Cancer Center discovered that high type 1 IFN causes lower NAD and NADH levels. Since NAD and NADH both play a role in cancer proliferation, finding out how to harness IFN could provide benefit to patients. Now, researchers may have found a way to effectively apply combination therapy for more effective pancreatic cancer treatment. Read the full study published in the Proceedings of the National Academy of Sciences.
The Research
Normally, both NAD and NADH play a role in metabolic processes. NAD stands for nicotinamide adenine dinucleotide. According to Elysium, NAD is:
required for fundamental biological processes to occur, but the body has a limited supply, as NAD+ levels decline with age. Secondly, NAD+ is a crucial requirement for the function of sirtuins, a group of proteins that are involved in critical cellular processes, including supporting a healthy metabolism and cellular energy production.
Elysium continues by explaining that NAD can be converted to NADH to:
[create] ATP during what’s called cellular respiration.
Researchers began testing how NAD depletion happened. During this, they discovered that cells with high type 1 IFN signaling were sensitive to, and thus more easily treated by, NAMPT inhibitors. They questioned whether using these inhibitors alongside STING agonists could stop the proliferation of pancreatic cancer cells. By using this combination therapy in mice models, researchers prevented pancreatic tumor growth and liver metastases (when the cancer spreads to the liver).
Typically, pancreatic cancer is difficult to treat because it is able to reprogram the metabolic network and harness cellular processes for cancer growth. In many cases, this cancer relies on NAD or NADH to stimulate growth. Now, researchers believe that identifying high IFN tumors, or finding a way to increase type 1 signaling, could be key to better treatment options moving forward.
Pancreatic Cancer
The exact cell mutation which causes pancreatic cancer, a cancer which forms in the pancreas, is unknown. However, the cell mutation causes the rapid proliferation of cancerous cells. Normally, your pancreas, which sits behind the lower part of your stomach, plays a role in blood sugar management and digestion through the release of hormones and enzymes. The most common form of pancreatic cancer (exocrine/pancreatic adenocarcinoma) occurs when cancers begin in the pancreatic ducts. Pancreatic neuroendocrine tumors, alternately, are a rarer form of pancreatic cancer which forms in the hormone-producing cells.
In many cases, this cancer is difficult to detect in early stages. In fact, many patients do not even show symptoms until advanced stages. Risk factors include a family history of pancreatic cancer, smoking, obesity, being older than 45 years old, and being male. Symptoms include:
- Unintended weight loss
- Abdominal and back pain
- Jaundice (yellowing of the skin and eyes)
- Dark urine or light stools
- Appetite loss
- Fatigue
- Nausea
- Pruritus (intensely itchy skin)
- Diabetes (new diagnosis or worsening of symptoms)
- Blood clots
- Depression and anxiety
- Bowel obstructions
- Pancreatitis (pancreatic inflammation)
Learn more about pancreatic cancer here.
