Project Summary/Abstract
Pancreatic cancer is the most common form of pancreatic cancer and is currently incurable. Unraveling essential
cellular reprograming required for PDAC development and progression, and further identifying new drug targets
to treat the disease is crucial to impact the outcomes for patients with this devastating disease. In this application,
we propose to study the function of transmembrane protein in regulating major nutrient supply routes by which
cells scavenge “food” to fuel their growth. It stands to reason that targeting such transmembrane protein will
block the nutrient supply of pancreatic cancer cells and result in cell death. Building on our strong expertise in
study transmembrane proteins in pancreatic cancer cell survival and growth, the overarching objective of this
proposed research is to gain a comprehensive understanding of the role of transmembrane protein in mediating
the nutrient supply routes and evaluate the potential of such transmembrane protein as a targeting node for
pancreatic cancer treatment. The major advantage of studying transmembrane proteins is their accessibility by
therapeutic agents, such as antibodies. To achieve the translational potential of our study, we will further develop
and characterize novel therapeutic agents direct target such membrane proteins in various new preclinical models
of pancreatic cancer. Upon completion of the proposed research, we will have more complete knowledge of the
extent to which pancreatic cancer is reliant upon transmembrane protein for nutrient salvage, how the nutrient
supply machinery is regulated by transmembrane protein on the surface in pancreatic cancer, and whether
targeting such membrane protein-mediated metabolic reprogramming may be potent to eradicate pancreatic
cancer cells. Answering these questions will significantly impact our ability to determine whether a rational
approach to therapeutically intervene in nutrient supply routes in pancreatic cancer exists. Furthermore, our
research is significant because it may have broad implications for other types of human cancers depending similar
nutrient supply mechanisms. In the short term, findings from this project will advance our understanding of the
nutrient supply routes required to sustain pancreatic cancer cells and provide strong preclinical evidence for
targeting the nutrient supply routes as therapeutic strategy in treating pancreatic cancer. In the long term, findings
of our research are expected to guide the development of clinical trials for achieving clinical benefits for patients
with pancreatic cancer. We believe that the results of our studies will have a positive impact on the general public
in the United States, benefiting individuals affected by pancreatic cancer and potentially leading to improved
outcomes and enhanced quality of life.