Publication Date

2019-12-12

Availability

Embargoed

Embargo Period

2021-12-11

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Cancer Biology (Medicine)

Date of Defense

2019-12-04

First Committee Member

Priyamvada Rai

Second Committee Member

Sulagna Banerjee

Third Committee Member

Vikas Dudeja

Fourth Committee Member

Karoline Briegel

Fifth Committee Member

Sundaram Ramakrishnan

Sixth Committee Member

Ashok Saluja

Abstract

Pancreatic cancer is a notoriously lethal disease. Late detection, lack of effective biomarkers, presence of a treatment refractory population of cells, an impermeable stroma, metastasis and tumor recurrence are some of the factors contributing to the dismissal 5-year survival rate of 8% for this disease. Hexosamine Biosynthesis Pathway (HBP) is a unique node in cancer metabolism. Its end product, UDP-GlcNAc is used by both tumor cells and the extracellular matrix component Hyaluronan for signaling, proliferation and metastasis of pancreatic cancer cells. While there have been reports examining the significance of HBP in individual factors contributing to tumor aggressiveness, a comprehensive study determining the “functional” importance of this pathway is lacking. In this dissertation, we determine the importance of HBP in maintaining the aggressive phenotype in pancreatic cancer, demonstrate actionable targets in the pathway and establish HBP as the quintessential achilleas heel of pancreas cancer.

Keywords

Pancreatic Cancer; Metabolism; Immunotherapy; Self Renewal; Hyaluronan; Hexosamine

Available for download on Saturday, December 11, 2021

Share

COinS