The Role of Mitochondria in ADT-Induced Sarcopenia in Prostate Cancer Patients
Abstract
Rationale, Objective, and Aims of the Application Prostate cancer (PCa) is the most common cancer among men and is even more common in the military and Veteran population. For patients with advanced PCa, the most common treatment includes lowering the levels of the hormone testosterone as much as possible. This is called androgen deprivation therapy (ADT). Unfortunately, ADT also causes patients to be fatigued, weak, and lose muscle. This is often referred to as “sarcopenia,” and it leads to falls, poor quality of life, and a higher risk of death. Currently, there is no treatment for sarcopenia because we do not understand the mechanisms that cause it. The mitochondria is the part of the cells responsible for providing energy to muscles, but to date, we do not know whether it is affected in PCa patients with sarcopenia due to ADT. The overall goal of this proposal is to establish whether the mitochondria is responsible for sarcopenia in patients with PCa receiving ADT. We will measure mitochondrial function, muscle mass and strength, feelings of fatigue, and quality of life in patients with PCa before starting and after 6 months of ADT. Applicability of the Research What types of patients will it help? Military personnel, Veterans, and civilians with PCa will benefit from the knowledge we will generate through this study. Other conditions associated with sarcopenia (advanced age, chronic lung or heart disease, other cancers) also happen more often in military personnel and Veterans, and men and women with these conditions will benefit from the knowledge that this proposal will bring. What are the potential clinical applications, benefits, and risks? This study will determine whether problems in muscle mitochondria cause sarcopenia after men receive ADT for PCa and will establish which patients are at higher risk for developing sarcopenia. A number of interventions targeting the mitochondria that are currently in clinical trials for other indications (including new drugs, such as elamipretide or acipimox) could be refocused to ADT-related sarcopenia if our study shows that mitochondrial function in muscle is affected by ADT. During this study, participants will receive a free evaluation of many aspects of their health. Patients will get reports regarding their body weight and composition, vital signs, and other chemistries at each visit. Another indirect benefit that patients may experience will be knowing how their fatigue and muscle function has changed as a result of ADT. They may also derive satisfaction from the knowledge that their participation has contributed to greater understanding of the links between ADT, fatigue, and quality of life. This information may even help them to discuss these issues with their doctors and make informed decisions regarding their therapy. The risks involved with the muscle biopsy, blood draw, exercise testing, X-rays, and completion of the questionnaires are considered minimal and to be outweighed by the potential benefits that this study will bring. What is the projected time it may take to achieve a patient-related outcome? The information gained in this study may help patients discuss these issues with their doctors and make informed decisions regarding their therapy right away. Patients may also decide to start exercising once they see how much their muscle function is being affected by ADT. Based on the results of this study, in 3 years, we may be able to predict who is at greater risk of developing sarcopenia after starting ADT. If this study shows mitochondria is the culprit for ADT-related sarcopenia, in 5-7 years, new therapies targeting the mitochondria might become available after they are tested in clinical trials. What is the likely impact of this study on addressing a central question or problem in PCa? We expect this study to have a great impact on survivorship and addressing the relative contribution of sarcopenia to the
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810461
Entities
People
- José M. Garcia
Organizations
- Seattle Institute for Biomedical and Clinical Research
- United States Army