Pancreatic Adenocarcinoma: An Analysis of Drug Therapy Options through Interaction Maps and Graph Theory
(1) BASIS Scottsdale High School, Scottsdale, Arizona, (2) Wright State University, Dayton, Ohio
Pancreatic cancer is the fourth leading cause of cancer-related deaths in humans (ASCO 2012). Pancreatic cancer cells exhibit a different gene expression profile from normal cells, with approximately 122 over-expressed proteins. A novel method was created to find the most important areas for future drug development based on influential disease-causing proteins in pancreatic cancer that currently lack drug treatments.
Protein-protein interaction maps were created, and proteins were ranked based on the number of connections each protein exhibited. A protein-drug interaction map was then constructed to analyze which influential proteins have no drugs developed for them or that have a very low drug association level. Afterward, the proteins were graphically and mathematically profiled to further determine which proteins are necessary for immediate research.
Through this method, KRAS, CDKN2A, and RBBP8 were found to be important proteins that lacked drug treatments. By comparing the chemical structure of KRAS to similar chemical structures of other GTPase enzymes and proteins with Walker A motifs, potential drugs were found that could inhibit KRAS and significantly slow the advancement of pancreatic tumors. This approach is applicable to several other types of cancers, such as renal cell carcinoma, melanoma, and prostate cancer.