HOXB13-Dependent Metastasis Suppression of Prostate Cancer by Proteoglycan Signaling
Abstract
As a son and son-in-law of prostate cancer survivors, I am keenly aware of the deficiencies in our ability to treat prostate cancer. The sole purpose of my research program is to develop new ways to combat prostate cancer, from early stage tumors to advanced metastatic disease. In particular, there is a dire need to provide surgeons and clinicians with more options for patients to aid in (1) whether to pursue surgery, radiation, or active surveillance after an initial diagnosis and (2) what to do when the cancer returns and progresses to metastatic disease. My laboratory has worked to accelerate the discovery of new biomarkers and drugs using bio-informatics, cell biology, publicly available patient-derived gene array datasets, and research collaboration to identify new signaling pathways in prostate cancer that can be translated into biomarkers and drug targets. In our ongoing work we have used bioinformatic, clinical, and molecular approaches to discover that MEIS proteins mark indolent, less-aggressive prostate tumors and that restoration of MEIS protein expression blocks tumor growth and metastasis. This prioritizes MEIS proteins as critical determinants of lethal, metastatic disease. Thus, understanding how they function has the high probability to identify new targets for therapy and to galvanize MEIS proteins as novel staging tools for men diagnosed with prostate cancer. The work proposed here has three main purposes: 1. To further understand how MEIS proteins block prostate cancer and identify new strategies for detecting indolent prostate tumors and treating advanced prostate cancers. 2. To understand how familial HOXB13 mutations, which occur in a small subset of prostate tumors, lead to increased tumor initiation and cancer aggressiveness. This has the high potential to help us devise new methods for preventing cancer initiation and slowing down metastatic progression. 3. To develop and characterize preclinical animal models that can be used to test agents targeting MEIS and downstream MEIS targets for clinical benefit. Therapies that increase MEIS expression could be used to save men from surgery or radiation, as well as utilized to halt the growth of advanced, metastatic tumors. It is my plan and sincere ambition that completion of the work proposed here represents a significant benefit to prostate cancer patients at both early and advanced stages of disease and also benefits future prostate cancer researchers.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010209
Entities
People
- Donald Vander Griend
Organizations
- United States Army
- University of Illinois at Chicago