Translating Novel Discoveries in Gastric Adenocarcinoma Biology into Therapeutic Advances
Abstract
Objectives and Rationale: This application is focused on pursuing three (of several) discoveries made by us during a prior grant period on gastric adenocarcinoma (GAC). GAC is a major health burden in the United States and globally, where there are over 1 million new cases per year, with 26,000 new cases expected in the United States. GAC is a leading cause of death in 10 countries. GAC is also relevant to our military personnel, Veterans, and their families. Even today, most patients are diagnosed in advanced stage and have a poor overall survival of less than 12 months. Therapies are quite limited in the clinic, and often it is a guessing game. Thus, much more research is needed before we can improve the outcomes of patients with GAC. Our objectives are to help develop the discoveries into practical therapies for patients with GAC. This will be a total departure from what happens in the clinics today, where patients are grouped by stage (and not by their cancer s molecular makeup), and every stage gets the same therapy but outcomes are poor and unpredictable. Thus we propose to change that and will focus on novel approaches. We are proposing entirely novel targets that are not being pursued and are discovered to be meaningful by us. These are (1) TRIM28/YAP1 crosstalk, (2) CCAT2/BOP1/AURKB axis with CIN, and (3) immunotherapy target, HSPA1L, as a unique protein on the cell membrane of GAC cells and not on normal cells. We are hoping to study each target in great detail in order to bring each one to the clinic to benefit all GAC patients, including military members, Veterans, and their families. Each target is relevant in all patients with GAC. It may be possible to combine them to derive greater advantage. The life of this project is 4 years, and we believe at the end of that time, some of these will be ready for early clinical development. We are entirely focused on GAC. This proposal will focus on GAC, and we will study samples that will come directly from our patients. The U.S. Department of Veterans Affairs considers GAC a Service-connected cancer from exposure to radiation. Additionally, U.S. soldiers living under field conditions are at greater risk of H. Pylori infections (classified as a class I carcinogen). The DOD (in a 2016 report to Congress published in September 2017) announced that GAC is associated with asbestos exposure, infectious agents (H. pylori, EBV, for example), and radiation exposure. It also stated that Service Members are increasing turning seropositive for H. pylori. It acknowledged that the majority of patients presenting with GAC have advanced, incurable condition and that there are no useful screening tests for GAC (exceptions are Japan and Korea, on a limited basis). The report stated that exposures are not only risky to Service Members, but also to their families and other beneficiaries. The cost of cancer care to the military for the year 2020 is projected to be more than $1 billion.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110668
Entities
People
- Samir M Hanash
Organizations
- The University of Texas MD Anderson Cancer Center
- United States Army