Stromal Modulation by the Secretory Factors of Neuroendocrine-like Prostate Cancer
Abstract
Applicability of the Research: Tumors in castration resistant prostate cancer patients are heterogenous, which contain different types of cancer cells (such as neuroendocrine, adenocarcinoma), immune cells, nerve cells and others. These cells communicate with each other, which is required for the metastatic progression of the disease. Since, metastatic dissemination of castration resistant prostate cancer is the root cause of death due to prostate cancer, we would like to understand the process of metastatic dissemination in this proposal by studying the communication between cancer cells and other non-cancer cells. Our preliminary studies have indicated that neuroendocrine-type prostate cancer can secrete several biomolecules that promote neuronal growth in the tumor and also help macrophages (a specific immune cell) to be activated following stimulation by the newly recruited neuronal cells. The activated macrophages then send signals to the cancer cells and transform them to become metastatic prostate cancer cells. In this proposal, we will study the mechanism by which neuroendocrine cancer cells promote neuronal growth in prostate tumor tissue. We will further study using animal models of prostate cancer, how neuron-macrophage axis in tumor tissue helps to generate metastatic and therapy-resistant prostate cancer, which leads to patient demise. A thorough understanding of this process will help to identify appropriate targets for drug development, which can prevent the metastatic dissemination of castration-resistant prostate cancer and thus can protect the lives of the patients from this lethal disease. Principal Investigator’s (PI) Career Goal in Prostate Cancer Research: As a young researcher, it intrigues me to undertake this challenge and study the biology of advanced Prostate Cancer (PCa) and its microenvironment that could be instrumental in designing better therapeutic approaches which could lead to improved survival and quality of life of PCa patients. In the proposed study I wish to seek the role of advanced PCa whether in altering the functions of stromal cells, such as nerve and macrophages in tumor microenvironment, which can then enhance the therapy resistance ability and metastatic dissemination of tumor cells. During the award period and beyond, mentors will provide guidance and suggestions to become oriented to the duties and responsibilities. Initial emphasis will be to improve scientific knowledge, experimental techniques, and design, as well as carry out hypothesis-driven research, followed by developing skills required for managing a project on a day-to-day basis, and I will be guided to analyze, interpret, and present data efficiently and articulately. Altogether, the PI intends to take advantage of this opportunity to establish her as an independent investigator in prostate cancer research. The outcomes of the study will make a significant contribution to the fight against prostate cancer in the future by exploring the biology of advanced PCa to reduce death. My multidisciplinary research training after successful completion of this proposal will establish me as an independent investigator and pursue PCa research. After completion of this award, I plan to expand my knowledge and utilize my research outcomes to devise therapeutic targets for advanced PCa and solve more deep-rooted mysteries behind aggressive PCa and therapy resistance.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310920
Entities
People
- Juhi Mishra
Organizations
- United States Army
- University of Nebraska Medical Center