This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Pancreatic cancer is an exceptionally aggressive cancer. One of the major factors contributing to the high fatality of pancreatic cancer is the poor response of most pancreatic cancer patients to therapies including radiation therapy and chemotherapy. Our long-term objective of this project is to understand the molecular mechanisms underlying the resistance of pancreatic cancer to therapies. We hypothesize that the mitochondrial proteins involved in reactive oxygen species (ROS) production or scavenging may be responsible for the resistance of pancreatic cells to therapies. Accordingly, we propose to use quantitative proteomic methods to systematically screen mitochondrial proteins that are involved in ROS production and scavenging in pancreatic cancer cells with different sensitivity to ROS inducing drugs. We are especially interested in identifying novel proteins/enzymes that can be targeted by ROS, inducing anti-cancer drugs to selectively kill cancer cells through ROS mediated apoptotic pathways.
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