Discover Novel Biomarkers/Targets for Advanced Gastric Adenocarcinoma Patients by Exploring Tumor-Associated Exosomes from Malignant Ascites
Abstract
Gastric adenocarcinoma (GAC) is a major health problem for our military personnel and their families. Military personnel, when deployed in a high-risk GAC area, acquire several risk factors and develop GAC at a higher rate than they do when they are back home. VA (Department of Veterans Affairs) hospitals have conducted studies on GAC and emphasized the need for developing better treatments. Additionally, advanced GAC is commonly diagnosed because we do not carry out procedures to detect GAC early. Advanced stage GAC patients have limited treatment choices, and their survival is often less than 10 months. The problem we are focusing on in this grant application is called peritoneal carcinomatosis (PC) (that is, cancer growing in the space in the abdomen where many organs are). In nearly 40% of patients with GAC, the cancer likes to travel to PC. Once it reaches there, it can grow fast and cause accumulation of fluid in the abdomen. Fluid accumulation is bad news because it needs to be drained (often repeatedly). Draining of the fluid leads to weakness, low blood pressure, loss of muscle mass, electrolyte imbalance, etc. Patients do not survive very long when they have PC. The treatment of PC is very limited and generally ineffective. We have developed an infrastructure to collect PC specimens. We are trying to take advantage of this resource and advanced technology to find novel treatments for GAC patients. We have been able to isolate small capsules in the fluid from PC. These capsules contain information that cancer cells like to use for their survival and travel. These capsules are called exosomes. We found exosomes in the PC fluid and the same exosomes in the blood of the patients. This is very exciting. In addition, we found a special protein in the exosomes called Galectin-3 (Gal3). Gal3 is dangerous for the patient. It can help cancer cells travel and grow. Gal3 also helps cancer cell to evade the immune system. We are focused on Gal3. However, we need to study more patients and also study all proteins and other molecules (like proteins or RNA) inside the exosomes. By being able to understand how cancer cells operate through exosomes, we may be able disrupt them. This will be an entirely a novel approach. We have found another use for Gal3, but this needs to be confirmed. Gal3, other proteins, and RNA could be used as flags to detect cancer when it is not obvious. Just to be clear, there are patients with GAC who do not apparently have PC but we collect washings (this is done through a surgical procedure called laparoscopy). We have noticed that even if no cancer cells are found in the washings, almost 25% of patients develop PC and die a miserable death. If we can detect PC early, it will open up new approaches (such as early treatment of PC might have an entirely different effect). We therefore will try to use exosome analysis in washings to see if Gal3 and other suspicious molecules are present when we “think” no cancer exists. Finally, our research will discover new targets that can be attacked and developed for patient care. Thus, we are using a very unique resource, unique approach, and hope to make a difference in the lives of GAC patients, military or otherwise.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810550
Entities
People
- Shumei Song
Organizations
- United States Army
- University of Texas at Austin