Discover Novel Therapeutic Strategies for Peritoneal Metastases from Gastric Adenocarcinoma
Abstract
Hypothesis: We believe that highly specialized stomach cancer cells travel to the peritoneal cavity (space inside the abdomen) and prosper there. These cells are most likely cancer stem cells that are capable of aggressive growth and are not affected much by currently available drugs. We believe that by detail studies (as proposed) of gastric cancer cells traveling to the peritoneal cavity, we can improve the outcome of these types of patients by identifying susceptibilities that can be targeted by new drugs. Objectives: Gastric cancer patients who develop peritoneal cancer have many symptoms and poor treatment options. We want to make some progress in this area. Therefore, we advance two objectives: (1) To find new susceptibilities in gastric cancer cells that live in the peritoneal cavity and document that we can control them effectively in animal and other models. Eventually, we will treat patients in the future with this new knowledge. (2) To validate such new findings in another unique group of patients with peritoneal carcinomatosis, and furthermore, we might also genetically engineer gastric cancer cells to travel to the peritoneal cavity; this will increase our understanding further and may open up improved treatment approaches. The Disease and Problems: Gastric cancer is rampant around the world with ~1 million new cases per year globally. The majority of gastric cancer patients are diagnosed at an advanced stage and have a short survival of ~9 months. Peritoneal carcinomatosis from gastric cancer is not an uncommon phenomenon (it occurs in ~40% of all patients). Systemic or intraperitoneal therapy is only transiently effective. Little research is performed in this area. Gastric cancer research has fallen far behind many other cancers. Most patients with gastric cancer under most circumstances are treated based on doctors’ experience and not often based on an individual patient’s or his/her tumor’s genomics. Therefore, the results of treatment are often disappointing. Patients and their family members are dismayed and disappointed when they learn what we have to offer. What Is Our Research and Who Can Be Helped: Our proposed research will provide new hope. It will help patients with gastric cancer whose cancer cells have traveled to the peritoneal cavity. First of all, we will work as a single team (three lab teams have already come together to make a commitment to improve the situation for this group of patients). We will apply sophisticated techniques (proteomic and genomics) to patient samples and perform integrative analysis to discover new targets for therapy. Second, in the future, we can try to easily find those targets in the next generation of patients to treat their cancer in a customized manner. We do not do that currently. Potential Clinical Applications: If we are successful, we can establish new therapeutic targets for the future generation of patients. Therefore, there is a good chance of considerable benefit. However, the only risk is that through a broad-spectrum profiling, the targets we will discover may not be relevant in our future patients (meaning we will not discover true targets). Another obstacle is that we may discover targets that are not common in most patients; this will reduce its importance. However, we remain hopeful that with three research teams involved and with a broad but sophisticated approach, we will find targets that will improve the outcome of our patients. Projected Time to Achieve a Patient-Related Outcome: We believe that this being a translational project (where we take specimen from cancer patients and discover novel target, we will be able to implement new knowledge to help our future patients immediately upon completion of this 3-year proposal). Peer Reviewed Cancer Research Program relevance: Gastric cancer is now listed in this Department of Defense program and our proposal is highly relevant as gastric cancer is a risk
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710466
Entities
People
- Samir M Hanash
Organizations
- United States Army
- University of Texas at Austin