Pancreatic cancer is a deadly and aggressive disease. The only option for metastatic pancreatic cancer is chemotherapy where only the antimetabolites gemcitabine (Gem) and 5-fluorouracil (5FU) are used clinically. However, resistance to these antimetabolites remains a problem highlighting the need to discover and develop new antimetabolites that will improve a patient’s overall survival. Cancer is a disease that has acquired numerous molecular, biochemical and cellular changes. Resistance to apoptosis is one of the characteristics of cancer, of which the inhibitor of apoptosis (IAP) family of proteins plays an important role. It has also been shown that cancer cells secrete vesicles called tumor exosomes (TEX) which are loaded with bioactive molecules which strongly influences the tumor microenvironment. Both protein and mRNA of the IAP Survivin, cIAP1, cIAP2 and XIAP are released into the extracellular space by not only the pancreatic cancer cell line PANC-1, but also from other cancer and non-cancer cell lines. IAP release may play an important role in pancreatic cancer’s lack of response to antimetabolite agents and eventual progression to chemoresistance. These findings can be used to design and develop novel compounds that can be used in combination with Gem or 5FU which are designed to target exosomes, in particular IAP packaging, which may make a vital impact in the treatment for metastatic pancreatic cancer.
School of Medicine
Wall, Nathan R.
Buchholz, John N.
Neidigh, Jonathan W.
Payne, Kimberly J.
Perry, Christopher C.
Doctor of Philosophy (PhD)
Year Degree Awarded
Date (Title Page)
Library of Congress/MESH Subject Headings
Neoplasms; Inhibitor of Apoptosis Proteins; Antigens - Neoplasm; Cell Line - Tumor; Cell Cycle; Exosomes; Vascular Endothelial Growth Factors; Equilibrative Nucleoside Transporter 1; RNA Interference; Matrix Metalloproteinases; Polymerase Chain Reaction
Subject - Local
Pancreatic Cancer; Metastatic Pancreatic Cancer; Tumor Exosomes; Antimetabolite Agents; Chemoresistance
Loma Linda University Libraries
This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.
Valenzuela, Malyn May Asuncion, "Existence of Inhibitor of Apoptosis in Tumor Exosomes" (2015). Loma Linda University Electronic Theses, Dissertations & Projects. 267.
Loma Linda University Electronic Theses and Dissertations
Loma Linda University. Del E. Webb Memorial Library. University Archives