Molecular Cross-Talk: Bone Metastatic Prostate Cancer and Nociceptive Neurons
Abstract
Prostate cancer is one of the leading causes of cancer deaths among men in the US and is diagnosed in 1 in 7 men over their lifetimes. Each year, approximately 40,000 men who "should" have been cured of their prostate cancer by surgery or radiation therapy present with incurable disease that has spread (metastasized) to the bone, usually years after primary treatment. Indeed, bone metastasis remains a major cause of death in prostate cancer patients. Why does prostate cancer become active in the bone? This deceptively simple question will continue to be the most important to answer for as long as we seek to end prostate cancer deaths. Furthermore, patients with bone metastases often suffer from significant bone pain. Cancer bone pain is the most common and vexing symptom of bone metastases. Since cancer bone pain can cause substantial impairment in quality of life, pain management is vital in improving treatments for patients with advanced prostate cancer. Current treatments for cancer bone pain using pain medicine have been somewhat successful; however, side effects and addiction are a serious and growing concern. Therefore, alternative drugs for cancer bone pain are urgently needed. Pain occurs when nerve fibers are irritated. Recent studies have hinted that interactions between nerve fibers and cancer cells facilitate cancer progression and metastasis, yet how these interactions influence cancer bone pain is still a mystery. The purpose of the proposed study is to determine how the interaction between metastatic prostate cancer cells and nerve fibers in the bone is involved in both the induction of cancer bone pain and the outgrowth of metastatic prostate cancer. Therefore, our two-part hypothesis is that (1) metastatic prostate cancer cells actively influence nerve fibers in the marrow, leading to bone pain, and (2) these same pain-induced nerve fibers simultaneously control tumor outgrowth. To address our hypothesis, we will use our innovative mouse models that enable us to measure cancer bone pain, tumor growth, and bone dynamics within the same animals. In addition, using biopsy samples from patients, we will verify the results from the animal experiments. The discoveries from our investigations will allow us to address the terrible challenges of bone metastases from new and different angles. More importantly, understanding the mechanisms involved can result in significant improvements in the care of advanced prostate cancer patients. If successful, this study will provide a strong foundation for clinical studies, leading to much needed better treatments and improved quality of life for cancer patients with bone metastases. We strongly believe that pain is not just a symptom of cancer and should not be treated as such. Instead, we propose that these pain signals can be targeted as new and effective treatments for the disease as a whole.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1710541
Entities
People
- Yusuke Shiozawa
Organizations
- United States Army
- Wake Forest University