Investigating the Therapeutic Potential of the ILEI/LIFR Pathway in Metastatic Breast Cancer
Abstract
Scientific Objective and Rationale: Despite significant advances in the treatment of primary breast cancer, diagnosis with metastatic breast cancer dictates a 3-year average survival rate. In fact, 90% of all deaths related to breast cancer are attributed to metastatic lesions. We have discovered an interaction between two proteins, ILEI and LIFR, that we propose allows cancer cells to leave the primary tumor, circulate through the body, and reform tumors at distant metastatic sites. Additionally, the protein LIFR contributes to the ability of breast cancer cells to remain dormant within the body for many years before developing metastatic disease. Our preliminary analysis indicates that preventing this interaction between ILEI and LIFR could be a valuable strategy for future drug design. Initially, we will analyze these proteins using cell culture and animal models to prove their significance in metastatic tumor initiation. Once we have thoroughly evaluated our protein complex in breast cancer models and further confirmed their vital role in metastasis, we will endeavor to inhibit the interaction. Using a high-resolution technique to study the surface of our proteins in detail, we will identify the essential points of contact for the ILEI/LIFR interaction and create a small synthetic protein to prevent complex formation. The experiments outlined in our proposal will investigate the potential for our newly discovered protein-protein interaction to be a drug target aimed to reduce and/or prevent breast cancer metastasis. Career Goals: My early training in blood vessel formation instilled an intense curiosity in the mechanisms by which cancer cells acquire the ability to metastasize through the blood stream. Herein, I have created a researcher development plan that will broaden my knowledge in breast cancer biology and provide me with the skills necessary to become an independent investigator at the forefront of metastatic breast cancer research. In addition to my personal scientific interest in the subject, I want to focus my efforts specifically on breast cancer metastasis as it results in the vast majority of breast cancer-related deaths. To this end, I joined the well-respected and productive cancer research laboratory of Dr. Philip Howe. Dr. Howe is an expert in the cellular processes that drive cancer cells to metastasize, and through his mentorship I will be able to cultivate a solid foundation in breast cancer biology and learn specific biological laboratory techniques. These are exciting techniques that I was not exposed to during my PhD training and will be essential for a career in breast cancer research. Furthermore, I have developed an important scientific relationship with my co-mentor, Dr. Shaun Olsen, who will continue to guide me through the complex technique of X-ray crystallography. Throughout my postdoctoral experience, I will attend scientific meetings to share my findings with the community and receive valuable feedback from outside investigators. Additionally, I will work with Dr. Howe and Dr. Olsen to publish our exciting results and train incoming undergraduate and graduate students in the background of our research and laboratory techniques. Because of the Breast Cancer Research Program Breakthrough Fellowship and the support of my valued mentors, I will have every opportunity to develop a strong foundation in oncology and the technical skills required to be a productive independent researcher. In my current research and in the future as the head of my own laboratory, I intend to explore potential therapeutic targets in metastatic breast cancer. Applicability and Impact: In the research proposed, we aim to address why some breast cancers become metastatic and why/how breast cancer cells lie dormant for years and then re-emerge. Unfortunately, metastasis is the leading cause of breast cancer deaths, yet no current therapies exist. Our ultimate goal outlined in this propos
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810003
Entities
People
- Annamarie Dalton
Organizations
- Medical University of South Carolina
- United States Army