Developing a MALDI/PET Early Warning Imaging System for Lethal Prostate Cancer
Abstract
Prostate cancer is a significant cause of mortality and morbidity in men. It is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Prostate cancer can not only behave differently between individuals, but the prostate cancer cells in a single tumor of a patient have a spectrum of aggressive potential that can be identified only on the molecular level, not at the microscopic level, as is conventionally done by pathologists. One example of this phenomenon is the presence of “neuroendocrine” molecules in prostate cancer that are associated with a very aggressive, treatment-resistant disease that is ultimately lethal. Unfortunately, there are no good methods to detect this phenomenon. Therefore, if we could develop a way to noninvasively detect and quantify the amount of aggressive disease in patients, we could better diagnose, develop more effective therapy options for, and extend survival for patients with prostate cancer. In this application, we will develop a new imaging system to detect a new class of molecules (chains of specific sugars or glycans) that can identify lethal variants of prostate cancer with positron emission tomography (PET) imaging. This imaging will allow us to identify more than just how much tumor is present in patients; it will allow us to identify and measure the amount of aggressive prostate cancer in patients. Because our goal is to establish the feasibility of this new imaging technology in this proposal, we will start with animal models. First, we will test our imaging technology in tumors grown in mice where the amounts of these molecules are known. Second, we will use this imaging to identify how these molecules are synthesized by aggressive tumor cells that will allow us to come up with better imaging and therapeutic strategies. Third, we will use imaging to characterize a new therapy that combines a drug that inhibits the synthesis of these molecules with immune therapy in mouse tumors. Thus, our application integrates new diagnostic and therapeutic strategies for prostate cancer. Although this application is entirely laboratory-based, we anticipate that the PET imaging that is proposed here, if successful, can be rapidly (2 years or less following completion of the award) translated to the clinical setting for clinical trials. Our institution has an established track record and infrastructure for translating PET imaging to humans. Furthermore, the drug that we are proposing has already been characterized and has the potential to enter testing for clinical trials as well. Although there are no risks to this technology, many benefits of this research exist, including characterization of a novel pathway by which lethal prostate cancers operate, a clinically relevant imaging system to detect lethal prostate cancer, and a potential imaging and therapeutic combination.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910795
Entities
People
- Joseph Ippolito
Organizations
- United States Army
- Washington University in St. Louis