Nature: Breakthrough! Reveal the molecular factors that genetic and environmental factors "collusively" promote pancreatic cancer!

February 5, 2021 // -- In a recent study published in the international journal Nature, scientists from the Memorial Sloan Kettering Cancer Research Center and others revealed how genes and the environment work together to play a key role in the development of pancreatic cancer.
As if weeds can grow in the crevices of the sidewalk, cancer usually occurs at tissue damage, which can be infection, physical damage, or some type of inflammation, the most common examples being stomach cancer induced by Helicobacter pyridosis, Barrett's esophageal tract caused by acid reflow, and even smoking-induced lung cancer.
Currently, researchers don't know how tissue damage conspires with genetic changes to promote cancer, and scientists' understanding of cancer is focused on the late stages of the disease, especially for cancers like pancreatic cancer, which is usually diagnosed in the later stages of the disease.
study, researchers focused on and analyzed the early stages of pancreatic cancer.
we can understand how tumors are formed, we may be able to intervene in their treatment before they progress to an incurable stage,' said dr. Direna Alonso Curbelo, a researcher at the University of London.
using advanced genomics techniques and innovative mouse models, the researchers revealed how tissue damage worked with specific genetic changes to promote early stage pancreatic cancer.
In the first step is to activate the normal repair process to react to the damage caused by the digestive enzymes of the body's pancreas itself, which the researchers say is like a mini-factory that makes enzymes that crush food, which, if released abnormally, lower the body's tissues, leading to inflammation of the pancreas.
Photo Source: Public domain but fortunately, the pancreas is very good at self-healing, and during the repair reaction, the cells in the damaged area change their behavior, temporarily halting the production of digestive enzymes and present in a different form;
But when these damaged cells contain mutations in the KRAS gene, the wound healing response gets out of hand and the cells fail to return to normal; the researchers note that we all know that mutated KRAS drives tumor growth in 95 percent of pancreatic cancer patients, but we don't know exactly how the mutated KRAS disrupts the wound healing process and causes disease.
researcher Alonso Curbelo said: 'We were able to identify at the molecular level the difference between the normal repair process and the cancer starting repair process, and we also found in damaged KRAS mutant cells that the way chromatin is organized may change uniquely.'
these changes, different genes are turned on or off, giving cells the characteristics of early cancer.
We can think of this process as opening and closing a zip file, where the part of the chromosome that should be open to normal pancreatic function is inadvertently reduced;
The whole process took place very quickly, and the researchers found that within 48 hours of tissue damage, more than half of the chromatin changes in advanced pancreatic cancer were already present in cells, because the changes in gene expression associated with these cancers were not caused by changes in DNA sequences, so they were called epigenetic characteristics.
The findings of this study are important because scientists can potentially block cancer progression by interfering with the activity of genes that are improperly turned on, and indeed researchers have shown that they can do this by "passivation" when they block the activation of damaged cells in mouse bodies.
interestingly, these early cancer-related changes do not occur when mutations in KRAS or tissue damage exist separately, and are induced only when they are combined. 'This study may help understand why cancer usually starts at tissue damage points; you may need a mutated gene and tissue damage to activate an oscic genetic process that drives the cancer to start, and a single action doesn't seem to make cancer happen,' said Lowe, a researcher at
.
The discovery and high specificity of osesogenal changes at the heart of cancer's starting point may help scientists try to target these newly opened genes as a way to selectively intervene and disrupt cancer progression.
future researchers may be able to use these genes as special markers to identify early signs of cancer and develop new therapies.
() Original source: Alonso-Curbelo, D., Ho, YJ., Burdziak, C. et al. A gene–environment-induced epigenetic program initiates tumorigenesis. Nature (2021). doi：10.1038/s41586-020-03147-x