Targeting the Cell Surfaceome of Aggressive Neuroendocrine Prostate Cancer
Abstract
Prostate cancer is a general term used to describe several different types of cancer involving the prostate. The most common form of prostate cancer is prostate adenocarcinoma. This type of prostate cancer is generally reliant on male hormones or androgens for growth and is initially responsive to treatments that block androgen production or action. Unfortunately, many men develop recurrent disease despite these hormone treatments and chemotherapy, and when their prostate cancer returns, it can reappear as a different type of cancer. One such form that emerges in up to 20% of men with lethal prostate cancer is called neuroendocrine prostate cancer. Neuroendocrine prostate cancer appears different from prostate adenocarcinoma and behaves much more aggressively, usually leading to death in affected men within a year. There are no good treatments that durably extend life in men with neuroendocrine prostate cancer. Neuroendocrine prostate cancer has been difficult to study because few biological models exist that can be studied in the laboratory. We have recently developed a new model in which we use normal human prostate tissues and convert them to neuroendocrine prostate cancer by introducing the cancer genes MYCN and an active form of AKT1. We have used this model to develop cell lines that can be readily grown and studied in the laboratory. We plan to establish several more neuroendocrine prostate cancer cell lines and make these available to the prostate cancer research community. Using available and newly developed prostate cancer cell lines, we have started to look at the protein molecules that are bound to the surface of neuroendocrine prostate cancer and prostate adenocarcinoma. In initial studies, we have found that the proteins on the neuroendocrine prostate cancer are quite different from those on the prostate adenocarcinoma. We believe that the proteins found on the surface of neuroendocrine prostate cancer may be useful targets for treatment as they are specifically expressed in these cancers and not normally found at high levels in most of the body. Specifically, proteins called antibodies that are normally formed by the body s immune system can be identified and engineered in the laboratory to bind these proteins on the surface of neuroendocrine prostate cancer. This targeted strategy has been used successfully to block or eradicate cancers, and multiple antibodies have been approved for use in humans as cancer therapy. We would like to complete the studies describing the proteins on the surface of neuroendocrine prostate cancer within one and half years. Then, we will start to develop antibodies that bind to these proteins, which will take approximately one and a half years to complete and characterize. These antibodies will be thoroughly tested to ensure that they bind to the target protein and no other unintended proteins in a variety of studies. Lastly, we will test whether these antibodies block the growth of neuroendocrine prostate cancer cell lines when grown in culture dishes or when grown in animals as tumors. If the antibodies are successful in blocking growth in these laboratory studies, we will plan to push these antibodies towards clinical studies to evaluate their effects in men with neuroendocrine prostate cancer. These studies will allow me to gain the scientific skills and knowledge to pursue a joint clinical and independent research career in prostate cancer. My goal is to investigate advanced prostate cancer in the laboratory in order to develop new, safe, and effective treatments for patients. This research proposal will give me the opportunity to work through the process of developing potential antibody therapies for neuroendocrine prostate cancer. I will actively engage in collaborations with leading experts in protein and antibody research at the University of California, Los Angeles and seek out experts at scientific seminars and meetings to develop the expertis
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710129
Entities
People
- John K Lee
Organizations
- United States Army
- University of California, Los Angeles