Mapping Elements of DNA Architecture Responsible for Malignant Transformation in Craniospinal Sarcoma
Abstract
Objective and Rationale: Chordomas are a type of sarcoma that arise from the head and spine. Because chordomas grow into the brain and/or around the spinal nerves, chordomas threaten neurologic function in patients. We currently do not have a chemotherapy that can effectively treat chordoma, so patients are treated with aggressive surgery, and if surgery is deemed too high risk, radiation. Most patients with chordomas will progress or develop metastases, and chordoma patients have an average survival of 5-10 years. This has created an urgency to develop new understanding and better options to treat patients with chordoma. Great effort has been placed to define markers that can be used to predict patient outcome, which will help identify which patients may benefit from adjuvant therapy and to identify new therapeutic targets in subsets of chordoma patients. A great barrier to identifying such markers has been the fact that chordoma is not caused by gene mutation, the most common cause of cancer. Our lab focuses on developing new ways of studying how DNA organization contributes to sarcoma formation using patient samples collected at surgery. Our objective is to understand how DNA organization contributes to chordoma formation and how we can take advantage of this to create new tests to predict tumor behavior and to develop new therapies. Career Goals of Principal Investigator: Dr. Andrew Venteicher is a physician-scientist at the University of Minnesota in the Department of Neurosurgery. He specializes in research and surgical treatment of patients with sarcomas of the head, neck, and spine. His career goals are to (1) use his unique position as a surgeon-scientist to advance the standard of care for patients with sarcoma, (2) develop a rigorous laboratory environment dedicated toward understanding non-traditional mechanisms of cancer formation to prevent and better treat sarcoma, (3) translate research findings into the clinic for patient care, and (4) help train the next generation of cancer researchers. In the fiscal year 2022 Peer Reviewed Cancer Research Program (PRCRP) Topic Area of Sarcoma, the FY22 PRCRP Overarching Challenge areas focused on in this proposal are to (1) elucidate the mechanisms behind cancer epigenetics/genetics and cancer development to improve prevention methods, and (2) evaluation from longitudinal collection of deep multidimensional characterization of clinically annotated research biospecimens during disease progression and treatment. This Career Development Award creates a rich environment to interact and learn from peers who are at the start of their careers in cancer research, the ability to network with senior members of the cancer research community, and provide for research time protected from clinical responsibilities. Interacting in this environment and formal mentorship by the Career Guide, Dr. Largaespada, an international leader in the study of molecular alterations in sarcomas and brain tumors, will accelerate the ability to transition to independence and become a future leader in sarcoma research. Specifically, this award will allow Dr. Venteicher to establish experimental and computational pipelines necessary to study epigenetic and nontraditional genetic mechanisms of sarcoma formation for future studies. Applicability of Research: Chordomas affect patients of all ages, with a propensity for aggressive chordomas to affect pediatric and young adult patients. Chordomas affect patients in all gender, racial, and ethnic groups. The proposed project will have direct benefit to patients with chordoma by (1) finding prognostic markers that can predict which patients may benefit from adjuvant treatments and (2) identify new vulnerabilities in chordoma based on studying DNA organization. In addition, this proposal is designed so that lessons learned in chordoma will teach us more broadly about mechanisms of tumor formation applicable to other sarcomas/cancers tha
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310432
Entities
People
- Andrew Venteicher
Organizations
- United States Army
- University of Minnesota