Fibrinogen Depletion Slows Pancreatic Cancer Growth & Spread | IU Research

Pancreatic cancer, one of the most aggressive and hard-to-treat cancers, may have revealed a new vulnerability. Researchers at the Indiana University Melvin and Bren Simon Comprehensive Cancer Center have discovered that reducing levels of fibrinogen – a clotting protein produced by the liver – can slow tumor growth and limit the spread of the disease in laboratory models. This finding, published recently in the journal Gastroenterology, offers a potential new avenue for therapeutic intervention in a cancer with a notoriously poor prognosis.

Fibrinogen and the Tumor Microenvironment

Fibrinogen is a key component in the blood clotting process. When an injury occurs, fibrinogen is converted into fibrin, forming the structural basis of a blood clot. However, this research, led by Melissa L. Fishel, Ph.D., demonstrates that fibrinogen also plays a significant, and previously underappreciated, role in the development and progression of pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer. The study showed that fibrinogen deposits on pancreatic tumors, actively contributing to their growth and shaping the environment surrounding them – what’s known as the tumor microenvironment.

The research team investigated the impact of reducing fibrinogen levels in mouse models of PDAC. Their findings were striking: lowering fibrinogen not only shrank the primary tumors but also significantly reduced their ability to metastasize, or spread, to the liver. Metastasis is a major driver of cancer-related deaths, and inhibiting this process is a critical goal in cancer treatment. Indiana University’s Simon Comprehensive Cancer Center is uniquely positioned to conduct this type of research, being the only National Cancer Institute-designated comprehensive cancer center in Indiana.

What Does This Imply for Patients?

It’s crucial to emphasize that this research is currently at a preclinical stage, meaning it has been conducted in laboratory models (mice) and has not yet been tested in humans. While the results are promising, they do not automatically translate to effective treatments for pancreatic cancer patients. However, the identification of fibrinogen as a potential therapeutic target opens up new possibilities for drug development and treatment strategies.

The study doesn’t suggest that patients should attempt to lower their fibrinogen levels independently. Fibrinogen is essential for normal blood clotting, and interfering with this process can have serious health consequences. Instead, the research points towards the potential for developing drugs that specifically target the interaction between fibrinogen and pancreatic cancer cells, or that selectively reduce fibrinogen activity within the tumor microenvironment.

Understanding the Study’s Design and Limitations

The study published in Gastroenterology utilized mouse models of PDAC to investigate the role of fibrinogen. Researchers genetically modified the mice to have reduced levels of fibrinogen production. They then compared tumor growth and metastasis rates in these mice to those in control mice with normal fibrinogen levels. The results consistently showed that lower fibrinogen levels were associated with slower tumor growth and reduced metastasis. The IU Simon Comprehensive Cancer Center has nearly 250 researchers conducting all phases of cancer research, from laboratory studies to clinical trials.

It’s important to acknowledge the limitations of this study. Mouse models, while valuable tools for cancer research, do not perfectly replicate the complexity of human pancreatic cancer. Notice differences in the biology of the disease between mice and humans, and a treatment that works in mice may not necessarily work in humans. Further research, including clinical trials in human patients, is needed to determine whether targeting fibrinogen can be an effective treatment strategy for pancreatic cancer.

Pancreatic Cancer: A Challenging Disease

Pancreatic cancer remains one of the deadliest cancers, with a five-year survival rate of just 11%. This low survival rate is due, in part, to the fact that the disease is often diagnosed at a late stage, when it has already spread to other parts of the body. Symptoms of pancreatic cancer are often vague and non-specific, making early detection difficult. The Indiana University Melvin and Bren Simon Comprehensive Cancer Center is a leading academic cancer research center in the United States, established in 1992 and designated by the NCI in 1999.

Currently, the primary treatment for pancreatic cancer is surgery, but What we have is only an option for a small percentage of patients whose tumors are localized and have not spread. Chemotherapy and radiation therapy are also used, but these treatments are often not effective in controlling the disease for long periods of time. The need for new and more effective treatments for pancreatic cancer is urgent.

Colon Cancer Awareness and Related Research

While this research focuses on pancreatic cancer, it’s worth noting that March is Colon Cancer Awareness Month. The IU Simon Comprehensive Cancer Center also conducts research into colon cancer, which is the third leading cause of cancer-related deaths in both men, and women. Increasingly, colon cancer is being diagnosed in younger individuals, highlighting the importance of screening and early detection.

What’s Next for Fibrinogen Research?

The findings from the Indiana University study are expected to spur further research into the role of fibrinogen in pancreatic cancer. Researchers will likely investigate the specific mechanisms by which fibrinogen promotes tumor growth and metastasis, and they will explore potential drug targets that can selectively disrupt these processes. Clinical trials will be essential to determine whether targeting fibrinogen can improve outcomes for pancreatic cancer patients. The center’s physician-scientists also oversee the care of Indiana children with cancer at Riley Hospital for Children, and influence care at 16 hospitals across the state.

The 14th Annual Chuckstrong Tailgate Gala, supported by the Indianapolis Colts and led by former head coach Chuck Pagano, will be held on April 17th, raising funds for cancer research at IU. This annual event demonstrates the collaborative effort needed to advance cancer treatment and improve patient outcomes. For sponsorship opportunities or tickets, contact Ashleigh Wahl at [email protected].