Aberrant Wound Healing Provides Insights in the Biology of Prostate Cancer Disparities
Abstract
Prostate cancer (PCa), particularly in African American men, is devastating to the person with the disease as well as to his family and community. For decades, researchers have sought to understand why the burden of this disease weighs so heavily on African Americans. Yet, no definitive answer has emerged, and new cases continue to mount. This study proposes a unique approach, one that is based on defining the environment of the cancer as opposed to the cancer itself and looking for surface manifestations not requiring invasive procedures to define. There are many similarities between cancer and how a wound heals. Both processes involve the same cell types, behaviors, and basic interaction. While they still possess some distinct differences, we believe that the commonalities between the two provide an opportunity for a novel approach: examine the wound response, not the prostate. For example, PCa aggressiveness is directly correlated to the amount of reactive stroma present in the tumor. Research has also shown that shown that African American PCa tumors have more extensive reactive stromas than those of European American (EA) men. Interestingly, during normal wound healing, a reactive stroma is also established to facilitate wound closure and an underlying remodeling process, thus the commonality between the processes that we exploit in this proposal. If we continue along these lines, we must also consider what happens in an abnormal setting. For example, some African Americans are predisposed to develop keloid scars. These are exuberant overgrowths of tissue that occur after an injury to the skin. This is abnormal wound healing. Interestingly, keloid scars share some characteristics with cancer in that cells will grow beyond the borders of the injury. Of course, they are not cancer, in that they do not spread to remote sites, but they do share some molecular features with reactive stromas. Therefore, we believe that one reason PCa is much more aggressive in African American men is due to the stroma — the same environment that permits growth of keloid scars. In this study, we will partner with a local African American-owned dermatology clinic to identify patients with and without keloids to understand what genes regulate their development. We will then determine whether this specific profile is associated with PCa risk. We will also explore the various cell types of keloid tissue to evaluate their capacity to alter the atmosphere into one that would permit the growth of cancer, specifically PCa. We are certain that the ramifications of this study will amply address the 2020 overarching challenges of reducing lethal prostate cancer in African Americans, Veterans, and other high-risk populations and help define the biology of lethal prostate cancer. For the first time, an indicator, keloid formation, may be identified as a risk factor that will drive increased vigilance and active surveillance, which will reduce death and consequently provide a potential platform for drug discovery as well as for testing future interventions.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110384
Entities
People
- Stacy Lloyd
Organizations
- Baylor College of Medicine
- United States Army