In Spain, pancreatic cancer is one of the most aggressive types of tumors and the third leading cause of death in our country, behind lung cancer and colorectal cancer. Although it is not one of the most common cancers, its high mortality is due to its late diagnosis and the lack of effective treatments. Around 80-90% of cases are diagnosed at an advanced stage.
This is why the international scientific community is working on different research models trying to find treatments capable of combating this aggressive disease, such as the one carried out by University of Massachusetts Amherst and Chan School of Medicine from the same university in the United States have succeeded in demonstrating in mice a new approach to treating pancreatic cancer.
The research, published in the journal Scientific translational medicinepresents the combined effects of a novel drug delivery system using nanoparticles, which activates an immunological pathway in conjunction with agents specifically directed against tumors.
The most common type Pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), with a relatively low five-year survival rate (13%), being the third leading cause of cancer death.
One of the biggest obstacles is the environment surrounding the tumorcharacterized by a dense tissue that forms a barrier around the tumor, preventing the formation of blood vessels and preventing the infiltration of immune cells.
“Drug delivery is a significant challenge due to the complex structure of the microenvironment of these tumors, which are notoriously difficult to treat,” he comments. Prabhani Atukoraleassociate professor of biomedical engineering at UMass Amherst and one of the study’s lead authors. Atukorale also points out that this environment prevents the activation and entry of immune cells into the tumor.
“Pancreatic cancer unfortunately does not respond well to most standard therapies, such as chemotherapy or even immunotherapy, which have revolutionized other cancer treatments over the last decade,” said Marcus Ruscetti, assistant professor of molecular, cellular and cancer biology. at UMass Chan School of Medicine, and co-author of the study.
Previous research has shown that two cancer drugs such as trametinib, a MEK inhibitor, can facilitate the growth of blood vessels, allowing greater entry of T cells and chemotherapy into the tumor. However, cancer has the ability to cheat to the immune system, making you believe that the tumor is just a group of normal, healthy cells. As a result, non-activated T cells They can’t eliminate cancer, although they are present in greater numbers.
To counter this, the researchers are looking to use their own approach. They are focusing on a pathway known as the stimulatory interferon gene (STING) pathway, which detects viral infections in the body.
“In case of infection,we exploit an anti-tumor immune response “very powerful for applying immunotherapy against the tumor,” explains Atukorale.
Scientists also want to activate the TRL4 pathway, because it enhances the effects of STING activation. They use agonists, chemicals that can induce a biological responsein this case, the activation of immunological pathways. However, getting these chemical agents into the tumor microenvironment remains a challenge.
This design also allows the two agonists to be packaged together, overcoming the difficulty of mixing them as they normally behave like water and oil.This ensures that both are transported simultaneously into the bloodstreamreach the same target cell and are absorbed together,” explains Atukorale.
“We use biocompatible lipid materials to encapsulate drugs that work together, even though they tend to repel each other. we use techniques engineering to add features that direct them to their specific destinations,” he adds.
The synergistic combination of the two agonists with T/P therapy proved effective: eight of the nine mice showed necrosis and tumor reduction. “Two mice even had complete responses, with the tumors completely disappearing, which is quite surprising,” Ruscetti explains.We have never observed this in this model.“.
“To move beyond pancreatic cancer to treat other types of cancer, a combination therapy is needed that attacks both the tumor and the immune system,” he concludes. Therapies for other cancers like PDAC that could be derived from this study include mutations in colon, lung, liver, and cholangiocarcinoma (bile duct cancer).
