Targeting Schwann Cell-Mediated Prostate Cancer Progression and Metastasis
Abstract
Rationale: Perineural invasion, a neoplastic invasion of nerves, is common in 75% of prostatectomy specimens of prostate cancer and in 11% to 38% of prostate cancer biopsies. For patients treated by prostatectomy, perineural invasion is predictive of extraprostatic extension, seminal vesicle invasion, positive surgical margins, tumor metastasis, and prognosis. Thus, targeting perineural invasion is an attractive therapeutic option. Previous studies have attempted to cut nerves surgically or chemically to block growth, occurrence, and metastasis of prostate cancers. However, shortcomings related to the side effects of these therapies hinder their clinical application. In the peripheral nervous system, Schwann cells (SCs) surround neurons and protect them. In prostate cancers, SCs promote perineural invasion, tumor metastasis, and bone metastasis-related pain. Thus, for patients with prostate cancer, targeting of SCs appears to be an effective approach to block tumor progression and metastasis and to relieve cancer-related pain. Objective: This study hypothesizes that targeting of SCs eliminates perineural invasion, inhibits tumor progression and metastasis, and relieves the cancer-related pain of prostate cancer. Specific Aims: There are two specific aims: (1) targeting of SCs to inhibit tumor progression and metastasis and (2) targeting of SCs to relieve bone metastasis-related nerve pain. This proposed work addresses one of the FY22 PCRP Overarching Challenges, Develop treatments that improve outcomes for men with lethal prostate cancer, which is relevant to the PCRP mission of eliminating death from prostate cancer and enhancing the well-being of Service Members, Veterans, and other men and their families who are experiencing the impact of the prostate cancer. Ultimate Applicability of the Research: Although this research is proposed for preclinical animal models, in future clinical applications, this developed approach is expected to prevent lethal tumor metastasis and relieve cancer-related pain for prostate cancer patients with bone metastasis. What Types of Patients Will It Help and How Will It Help Them? This study will help (1) men with intermediate-risk and locally advanced prostate cancer who have perineural invasion diagnosed by prostate cancer biopsies and/or (2) men with high-risk prostate cancer who have bone metastasis. Targeting of SCs in this research will help patients (1) by preventing and reducing tumor progression and metastasis and/or (2) by relieving cancer-related pain from bone metastasis. What Are the Potential Clinical Applications, Benefits, and Risks? The potential clinical applications of this research are to improve existing therapeutics by (1) eliminating perineural invasion through targeting of SCs and preventing metastasis by (2) targeting SCs in bone to relieve cancer-related pain with few side effects, which will benefit patients with prostate cancer. Since this is a previously undeveloped therapeutic approach, potential risks will be addressed in this research. What Is the Projected Time It May Take to Achieve a Patient-Related Outcome? In the proposed study, if the developed therapeutic approach is effective with limited side effects in preclinical animal models, it will be immediately advanced to a clinical trial.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310313
Entities
People
- Lizhong Wang
Organizations
- United States Army
- University of Alabama at Birmingham