Analysis of Gastric Adenocarcinoma Data in a Pan-GI Context to Reveal Genes, Pathways, and Interactions that Yield Novel Therapeutic Advantages

Principal Investigator: AKBANI, REHAN
Program: PRCRP
Proposal Number: CA150252
Award Number: W81XWH-16-1-0237
Funding Mechanism: Career Development Award
Partnering Awards:
Award Amount: $565,219.82


Objectives: The goal of this project is to study stomach cancer to reveal new insights into the biology of the disease that could potentially have therapeutic implications. In my previous work, I and my collaborators have identified novel interactions among sets of related genes (i.e., pathways) in stomach and other gastrointestinal (GI) cancers. We have identified certain subgroups of stomach cancer patients where those interactions may be exceptionally abnormal and lead to worse survival. The interactions and corresponding sets of genes may be targetable by existing drugs and/or drugs under development for treatment of that subgroup of stomach cancer patients. Other subgroups have other interactions and genes that may also be targeted using different drugs. In that way, we can potentially give customized regimens of drugs to specific patients whose cancers exhibit targetable characteristics. The objective of this research is to find those targets and improve our understanding of the biology of stomach cancer. We will borrow information from other related cancers as well, i.e., other GI cancers, to improve our chances of finding those targets.

Principal Investigator's (PI) Career Goals: The PI, Dr. Rehan Akbani, is a tenure-track Assistant Professor at the University of Texas MD Anderson Cancer Center in Houston, Texas. As a junior professor at the nation's top cancer hospital (according to US News and World Report), Dr. Akbani is committed to a career in cancer research with a focus on stomach cancer. He is also a prominent member of The Cancer Genome Atlas (TCGA) project, the largest cancer research project in US history, and the Co-Director of MD Anderson's TCGA Genome Data Analysis Center (GDAC). As part of TCGA, he has co-authored numerous high-profile papers, including one on stomach cancer. Research from the proposed project will advance his career by increasing the number of stomach cancer publications where he has made major contributions. Not only will the resulting publications advance the field of stomach cancer, but it will also help Dr. Akbani in achieving tenure and securing future funding for further stomach cancer research. The proposed career development plan will enable him to work closely with and seek the tutelage of senior professors, like his designated mentor, Dr. Ajani, who is a well-established stomach cancer oncologist; Dr. Hofstetter, who is another experienced oncologist; and Dr. Weinstein, who is the chair of Dr. Akbani's department of Bioinformatics and Computational Biology at MD Anderson. All of those factors will help Dr. Akbani in his ultimate goal of becoming at the forefront of stomach cancer research.

Applicability of the Proposed Research: The proposed research is designed to find potential drug targets in patients with stomach cancer. It relies on the theory that every patient's cancer is molecularly distinct and one-size does not fit all when it comes to cancer therapy. Each patient should be given drugs that are specific for his/her type of stomach cancer. The research will attempt to find multiple potential targets, not just one or two, any number of which may be targeted by drugs that are already on the market or in clinical trials. The benefit is that we can effectively use existing drugs for stomach cancer therapy in those patients who are predicted to respond well to the targeted treatment. The side effects of most of those drugs would presumably be known, so the risks can be better managed. At the end of the 3-year research, it is expected that the molecular targets would be identified, after which point further research can be conducted to determine the efficacy of the drugs that work against them.

Benefit to Military Personnel and Their Families: Stomach cancer is highly relevant to our troops and their families. Our troops have been engaged in endemic areas of stomach cancer (Japan/Korea/Taiwan) and are susceptible to high-risk region specific factors (e.g., stomach cancer causing viruses, pickled food with carcinogens, and high-salt diet). In addition, researchers have reported an increase in the risk of stomach cancer among younger individuals, which imposes another health risk to military families. This research will expand our knowledge of stomach cancer and potentially improve treatment options for the military and their families by discovering novel targets for therapy.