Understanding the Extracellular Vesicle-Mediated Mechanism(S) of Resistance in Advanced Prostate Cancer
Abstract
Prostate cancer is a slow-growing disease. Despite effective treatment by surgery or radiation therapy when detected early, around 25%-40% of patients undergo relapse. Since prostate cancer cells need a hormone called androgen to grow, a common form of treatment involves limiting the amount of this hormone using drugs that interfere with its production. While this treatment is initially effective in most patients, the tumor recurs in many patients within 2 years. It is known that the prostate cancer cells secrete tiny fragments called vesicles. These are known as extracellular vesicles, and they contain protein, lipid, and small RNA, which resemble the original cells. The extracellular vesicles have been shown to be involved in communication between cells and their environment. These extracellular vesicles are involved in tumor growth and metastasis. We believe that by studying how the extracellular vesicles are made in the cells, we will be able to understand the processes by which these vesicles help prostate cancer cells to grow. This will have the potential to provide a new target for therapy, which will overcome cells that are growing despite a low amount of androgen in their environment. Our experiments will examine late-stage prostate cancer cell lines isolated from patients. These can grow in a tissue culture dish or in culture in the presence of human bone cells to simulate a 3D environment. We will study whether by disrupting the function of extracellular vesicles, we alter the growth of prostate cancer cells and whether they can induce prostate cancer cells to grow in the bone environment. By characterizing the extracellular vesicles secreted by prostate cancer cells, we hope to be able to differentiate patients who will be more sensitive to androgen deprivation therapy from those who won t respond and therefore minimize administration of drugs to non-responding patients. The extracellular vesicles can be isolated from a patient s blood sample. This study will allow us to understand the biological processes happening in the patients who suffer from late-stage prostate cancer and to help tailor the design of individualized therapy that might benefit them. Sampling blood from patients in the future, which is relatively non-invasive, gives the ability to further validate our work. This study could have a large impact on patient outcomes by improving individual treatment selection and quality of life; this will also have a significant impact on the overall health economy. Knowledge from this study will help me to contribute to new drug delivery strategies for improving individual, personalized treatment in the future.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610736
Entities
People
- Carolina Soekmadji
Organizations
- Queensland University of Technology
- United States Army