Pancreatic ductal adenocarcinoma (PDAC) is almost uniformly lethal 1, with overall 5-year survival rates of ~8% that have remained constant over time 2 while global incidence is increasing 3. Metal compounds have shown efficacy in treating cancer since the 1960s with the advent of cisplatin 4; and a randomized phase III trial has demonstrated that PDAC treatment using gemcitabine and cisplatin compared to gemcitabine alone led to improvements in median overall survival and progression-free survival 5. A growing library of metal-based chemotherapeutics have been developed and applied to many different cancers 6, and it is generally accepted that the ECM plays the dominant role in restricting the delivery and binding of these DNA intercalating drugs 7. As such, many new combination therapies propose inclusion of ECM remodeling drugs 8. Despite these hypotheses, there currently exist no technologies capable of measuring either ECM or metal compound specific binding in large-field-of-view (millimeters) tumor sample imaging. This project aims to allow ECM and metal compound specific binding to be measured in large field-of-view tumor sections through two innovations that are adaptable to numerous other tumor biology

The specific research goals for students are to be able to:

·         Understanding the effects collagen has on x-ray diffraction (XRD) and working with algorithms that enable quantification of collagen in pancreatic cancer specimens using XRD.

·         Learning to use optical and x-ray fluorescence to quantify drug deposition and binding in pancreatic cancer specimens.

·         Identifying connections between pancreatic cancer extracellular matrix and drug delivery and binding.

The specific learning goals for students are to be able to:

·         Use XRD data to map collagen content and orientation in biological tissue.

·         Use optical and x-ray fluorescence with paired-agent imaging kinetic models to quantify drug delivery and binding.