Prevention of Hair Loss in Ovarian Cancer Chemotherapy
Abstract
Paclitaxel is a key drug used in chemotherapy treatment of several solid tumors including ovarian cancer. While often highly effective, paclitaxel has major adverse effects, namely sensory neuropathy and severe hair loss (alopecia). Since alopecia is psychologically devastating for many patients, preventing paclitaxel-induced alopecia is a major, as yet unmet need in clinical oncology with a massive impact on quality of life for cancer patients. Paclitaxel causes hair loss by stabilizing microtubules in the highly proliferative hair matrix keratinocytes, resulting in cell death, hair follicle dystrophy, and obliteration of the hair follicle’s capacity to regenerate. While hair loss may be reduced by scalp cooling to reduce drug exposure in some patients, the benefit is limited and unpredictable. Therefore, the development of satisfactory methods to reliably prevent paclitaxel-induced alopecia is an urgent, unmet medical need. We have made the unexpected discovery that a brief exposure to low intensity ultrasound can effectively neutralize the cytotoxic effects of paclitaxel on cultured cells by disrupting paclitaxel-induced rigid microtubule bundles, thus preventing cell death. Therefore, we propose here to rigorously test whether low intensity ultrasound can prevent the hair follicle cytotoxicity of paclitaxel in both human scalp hair follicle organ culture and mouse models. The current proposal is to study mechanisms and to develop a method to prevent hair loss (alopecia) for ovarian cancer patients undergoing chemotherapy treatment. The finding may benefit quality of life issues for ovarian cancer patients. The research project will address the following FY22 OCRP Areas of Emphasis: 1. Develop novel therapeutic strategies for treatment and prevention. 2. Identify and implement strategies to improve OCRP’s survivorship and quality of life. The ultimate goal is to translate the research results into a clinical protocol designed to utilize ultrasound to prevent paclitaxel-induced hair loss in cancer therapy using paclitaxel and other microtubule stabilizing agents. Since low-intensity ultrasound has been widely used in medicine with an excellent safety profile, the development of ultrasound treatment to prevent paclitaxel-induced alopecia is highly practical and feasible. Our study will provide proof-of-principle and critical guidance for the optimized utilization of ultrasound therapy to effectively prevent hair loss (alopecia), thus greatly improving the quality of life of cancer patients. If the laboratory results are positive, we will plan the incorporation of low intensity ultrasound to enhance paclitaxel in ovarian cancer chemotherapy in clinical procedure. Since low intensity ultrasound is widely used in medicine and has an excellent safety profile, the addition of ultrasound to chemotherapy will be highly feasible and practical, and a clinical trial will be achievable within a few years. The current proposal has a near term impact on the prevention of hair loss in the treatment of ovarian and additional metastatic and drug- refractory cancer. Our study will provide proof-of-principle and critical guidance for the optimized utilization of ultrasound therapy to effectively prevent alopecia, thus greatly improving the quality of life of cancer patients. The ultrasound treatment to prevent hair loss will benefit ovarian cancer patients from both civilian population and the health care needs and welfare of military Service Members, Veterans, and their families.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310260
Entities
People
- Xiangxi Xu
Organizations
- United States Army
- University of Miami