In the medical field, there has been a dilemma about how to reverse the fibrotic wall around pancreatic tumors. And a new study may offer a breakthrough strategy for pancreatic cancer. This study found that a class of drugs known as HDAC inhibitors has the potential to become a new hope for pancreatic cancer by interfering with the activity of fibroblasts**.
According to a study published in Nature Communications on December 6, 2023, scientists at the Salk Institute have discovered this new pathway.
Professor Ronald Evans, director of Salk's Gene Expression Laboratory and one of the study's senior authors, said: "These drugs are not only effective against the tumour itself, but also on the fibrous tissue surrounding the tumor. This can be an extremely effective method for pancreatic cancer. ”
Under normal circumstances, in response to the appearance of pancreatic tumors, the pancreas normally activates fibroblasts – the cells that make up the walls of scar tissue. When fibroblasts are activated, they form a thick layer of scar tissue that tries to isolate the cancer and stop it from spreading. However, cancer uses these signals to promote growth.
The new study explores the effects of a drug called a histone deacetylase (HDAC) inhibitor on fibroblasts. These drugs alter the structure of DNA within cells, making certain DNA fragments more difficult to access and read by other molecules. Thus, targeting HDAC can control cellular behavior, such as the growth of cancer cells.
Co-corresponding author Michael Downs explains: "In most pancreatic cancers, fibroblasts play both good and bad roles, which is a double-edged sword. ”。
In experiments, researchers have found that HDAC inhibitors can block the activation of fibroblasts and inhibit tumor growth. "These inhibitors actually have two effects, both reducing tumor growth signals and reducing the actual activation and accumulation of fibroblasts. ”。
In animal experiments, researchers have also found that an experimental HDAC inhibitor called entinostat not only reduces the activation of fibroblasts around pancreatic tumors, but also slows tumor growth. In addition, the researchers also analyzed data from pancreatic cancer patients and found that the higher the HDAC1 level in the fibrous tissue surrounding the tumor, the worse the patient's** outcome.
"This is consistent with the results we observed in our experiments," the researchers noted. If HDAC activity is higher in fibroblasts, the patient is also in worse condition. ”。
Studies have also found that HDAC inhibitors can block the expression of several genes, suggesting that these drugs can target these genes to block the activation of fibroblasts, thereby inhibiting the development of cancer growth and fibrosis.
"In the past, there was debate about whether targeting fibroblasts for pancreatic cancer was good or bad, as there was evidence that completely eliminating fibroblasts could make the cancer more aggressive," said Annette Atkins. But our findings suggest that we don't need to get rid of them completely, just restricting their activation is beneficial enough. ”
Nonetheless, more work is needed to determine how best to deliver HDAC inhibitors to the dense fibrous tissue surrounding pancreatic tumors and how best to combine them with other cancer** protocols. This breakthrough study has brought a new dawn to the development of pancreatic cancer, but further in-depth research and exploration are still needed in clinical applications.