Recently, scientists have been exploring a more genetically-based underlying cause of pancreatic cancer. Now, according to Medical XPress, researchers are deepening their understanding of genetics and pancreatic cancer in relation to drug development. Researchers from the Perelman School of Medicine at the University of Pennsylvania recently discovered that MYBBP1A gene mutations, which occur in up to 66% of all pancreatic cancer cases, make tumors more susceptible to PARP inhibitors. Read the full findings in Science Advances.
PARP Inhibitors
According to the National Cancer Institute (NCI), PARP inhibitors:
are a type of targeted therapy [that] blocks an enzyme in cells called PARP [which] helps repair DNA when it becomes damaged. In cancer treatment, blocking PARP may help keep cancer cells from repairing their damaged DNA, causing them to die.
Typically, PARP inhibitors are used to treat ovarian and breast cancer. However, scientists determined that inhibiting PARP prevents cell growth. Currently, MYBBP1A mutations allow cells to grow at an unchecked rate. Ultimately, researchers determined that chromosome 17 deletions, alongside one deficient MYBBP1A gene, caused significantly cancerous cells to grow. Thus, knocking out the remaining MYBBP1A copy could prevent further pancreatic tumor development.
Through further researchers, scientists discovered that MYBBP1A proteins interacted with PARP1 proteins when promoting cellular growth. This suggested that PARP1 inhibitors could be beneficial in combatting pancreatic cancer. In particular, scientists were drawn to niraparib and olaparib, both of which remove MYBBP1A from cells when trapping PARP1. So, in this sense, olaparib and niraparib seem to act in the same way as gene editing would – by knocking out MYBBP1A. In mouse models of pancreatic cancer, olaparib reduced tumor growth.
Of course, further studies should be done to affirm these findings. Currently, the scientists from Perelman School of Medicine are working with Dr. Kojo Elenitoba-Johnson, MD, to create a new diagnostic test to help determine which patients might benefit from this specific treatment.
Pancreatic Cancer
When healthy cells develop abnormalities, they can eventually grow at an uncontrolled rate, developing into cancer or a tumor. In the case of pancreatic cancer, this cell mutation and proliferation occurs in the pancreas, an organ that sits behind the lower area of the stomach. Normally, the pancreas releases enzymes and hormones that play a role in digestion and blood sugar management. However, pancreatic cancer can inhibit these functions. There are various types of pancreatic cancer depending on the area of development. For example, Islet cell tumors develop in the pancreas’ neuroendocrine cells, while pancreatic adenocarcinoma occurs in the cells which line the pancreatic ducts.
Typically, pancreatic cancer affects those over 45. It is also more common in males than females. Other risk factors include obesity, smoking tobacco, and a family history. An estimated 60,000 new cases of pancreatic cancer are diagnosed each year. In many cases, patients with pancreatic cancer will be asymptomatic until later disease stages. As a result, pancreatic cancer has a high mortality rate following diagnosis. When symptoms do appear, they include:
- Pruritus (intense itching)
- Diabetes
- Unintended weight loss
- Appetite loss
- Fatigue
- Nausea
- Depression
- Blood clots
- Jaundice (yellowing of the skin and eyes)
- Abdominal and back pain
- Dark urine and light stool
- Bowel obstructions
Learn more about pancreatic cancer.
