According to a story from Science Daily, a team of scientists affiliated with the Salk Institute recently published a study on December 6, 2023 focused on how a class of therapies called HDAC inhibitors could be used to treat pancreatic cancer, one of the deadliest forms of cancer. This study was published in the academic journal Nature Communications.
About the Study
There are a number of factors that make pancreatic cancer particularly challenging to treat effectively, let alone cure. One such factors is the pattern of scarring that is common in the disease. Pancreatic cancer tumors frequently exhibit heavy fibrosis (scarring), creating a layer of thick tissue that surrounds the tumor and is able to prevent many common cancer therapies from reaching it.
The pancreas releases fibroblasts–connective tissue cells– as a response to the development of a pancreatic cancer tumor. This is an immune response that is intended to isolate the tumor and prevent its spread, but the signaling molecules released by fibroblasts are highjacked by the cancer and used to facilitate its own growth.
The study evaluated the effect of histone deacetylase (HDAC) inhibitors on the activity of fibroblasts. HDAC plays a vital role in making changes to the 3D structure of DNA within a cell. An HDAC inhibitor would prevent a cell from making major changes to its DNA structure and behavior—such as the erratic, out of control growth of a cancer cell.
In a test on isolated cells in a lab setting, HDAC inhibitors prevent fibroblasts from activating and entering a tumor-supportive state. In a pancreatic cancer mouse model, an HDAC inhibitor called entinostat reduced fibroblast activation at the tumor site and slowed growth of the tumor.
The team also looked at data from pancreatic cancer patients and found that elevated HDAC1 levels in the scar tissue were more prevalent in cases with the worst outcomes. The scientists also identified multiple genes that HDAC inhibitors prevented from getting expressed and suggested that future therapies could target them as a way to shut down fibroblast activation.
Prior studies have revealed that destroying fibroblasts is detrimental and can allow the cancer to grow more rapidly. However, the findings from this study suggest that inhibiting the activation of these cells appears to be beneficial.
About Pancreatic Cancer
Pancreatic cancer is one of the most dangerous forms of cancer. The disease affects the pancreas, which is a glandular organ that is situated behind the stomach. Part of the reason that pancreatic cancer is so dangerous is that it rarely produces noticeable symptoms until it has reached an advanced stage and begun to spread. However, even when detected earlier, it is difficult to treat effectively. Risk factors include being male, old age, African American ancestry, family history, smoking, obesity, diabetes, chronic pancreatitis, and a diet heavy in red meat, processed meat, or meat cooked at very high temperatures. Symptoms include depression, upper abdominal pain, jaundice, diabetes, constipation, weight loss, and appetite loss. Treatment approaches for this cancer include surgery, chemotherapy, and radiation therapy. Even with heavy treatment, pancreatic cancer almost always returns. The five-year survival rate is just 10%. To learn more about pancreatic cancer, click here.
